Ruth Boggs, MA, CT
`ATA-Certified Translator (#62196) & Interpreter | Tel.: 703.378.9305 | rutheboggs@gmail.com
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`Laborbuch = Lab journal
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`HIGHLY CONFIDENTIAL
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`GRT-NUC00074243_T
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`Page 1 of 10
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`Grunenthal GmbH Exhibit 2033
`Rosellini v. Grunenthal GmbH
`IPR2016-00471
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`

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`Ruth Boggs, MA, CT
`ATA-Certified Translator (#62196) & Interpreter | Tel.: 703.378.9305 | rutheboggs@gmail.com
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`Laborbuch = lab journal
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`HIGHLY CONFIDENTIAL
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`GRT-NUC00074244_T
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`Page 2 of 10
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`Ruth Boggs, MA, CT
`ATA-Certified Translator (#62196) & Interpreter | Tel.: 703.378.9305 | rutheboggs@gmail.com
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`HIGHLY CONFIDENTIAL
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`GRT-NUC00074245_T
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`Page 3 of 10
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`Ruth Boggs, MA, CT
`ATA-Certified Translator (#62196) & Interpreter | Tel.: 703.378.9305 | rutheboggs@gmail.com
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`Lab journal No.: ** 2186 **
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`HIGHLY CONFIDENTIAL
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`GRT-NUC00074246_T
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`Grünenthal GmbH
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`Lab Journal
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`Department:
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`GPR – TD – PD
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`Laboratory area:
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`Dr. Griebel
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`User / project:
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`Date issued:
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`Date turned in:
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`MUELLER
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`September 29, 2009
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`October 18, 2010
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`Page 4 of 10
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`Ruth Boggs, MA, CT
`ATA-Certified Translator (#62196) & Interpreter | Tel.: 703.378.9305 | rutheboggs@gmail.com
`
`CONFIDENTIAL
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`[Grünenthal logo]
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`User guidelines for maintaining a lab journal:
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`1. The objective of this lab journal is to protect all patentable
` Grünenthal inventions from the time when they were made (first
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`inventor principle). The idea for, the implementation of, and the
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`continuous work on the invention must be reproducible. Therefore, the
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`lab journal contains all of the user’s experiments and observations. All
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`entries (descriptions of methods, reaction conditions, results) shall
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`appear by date and in the order they were performed/made.
` To maintain continuity, it is important to document all downtimes such
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`as sick leave, vacation, equipment failure, ordering material, work on
` multiple projects, etc. by entering them into the lab journal.
`2. Please start each entry with the date and the first three places of the
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`project code (if possible). Please end each daily entry with date and
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`signature. All entries are made on front and backside, without gaps,
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`legibly, with ink pen, ballpoint pen, or magic marker (blue or black;
` waterproof pen).
`3. Please enter all descriptions, specifications, materials and results
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`related to the experiment in the precise order of dates. The objective
` must be that any employee can continue and/or reproduce the work. If
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`applicable, please glue any sheets of findings or results into the lab
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`journal and sign them in such a manner that the signature spans from
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`the glued-in sheet to the lab journal page. Voluminous records may be
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`collected separately. The lab journal must contain an appropriate
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`reference to this collection of documents.
`4. Please make sure that errors are crossed out and dated and initialed.
` Retroactive changes must bear the current date and initials and be
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`signed by the head of the laboratory.
`5. Each page must be initialed by the responsible head of the laboratory
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`and reviewed and countersigned by a knowledgeable witness who
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`does not report to said head of laboratory and is not involved in the
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`project.
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`6. A table of contents may be prepared.
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`7. Please turn in lab journal for central archiving after completion, but no
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`later than the time period laid down in SOP HQ-DI-110-0055-ff. New
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`lab journals are issued by the central archive. Any copies for personal
`use should be prepared prior to turning in the lab journal.
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`8. The lab journal must be kept in a safe place and is intended for
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`internal use only. Please notify your head of laboratory immediately in
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`case of loss of a lab journal. The lab journal must be kept under lock
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`and key during non-work hours.
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`HIGHLY CONFIDENTIAL
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`GRT-NUC00074248_T
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`Page 5 of 10
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`

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`Ruth Boggs, MA, CT
`ATA-Certified Translator (#62196) & Interpreter | Tel.: 703.378.9305 | rutheboggs@gmail.com
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`CONFIDENTIAL
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`[Grünenthal logo]
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`Page
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`March 24, 2010
`(Initialed)
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`Table of Contents
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`Table of Contents, Lab Journal 2186
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`Page Batch
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`HIGHLY CONFIDENTIAL
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`GRT-NUC00074248_T
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`Page 6 of 10
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`Ruth Boggs, MA, CT
`ATA-Certified Translator (#62196) & Interpreter | Tel.: 703.378.9305 | rutheboggs@gmail.com
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`CONFIDENTIAL
`[Grünenthal logo]
`75 Page 1 of 2
`Project: ________________________________ Lab journal No. ** 2186 **
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`[Stamp: “Dec. 18, 2009, Initialed”]
`Experiment Name: PG1026-001
`Experiment Label: Methoxy cleavage
`Creation Date: Wednesday, Dec. 2, 2009
`Project Number: AHW
`Project Name: CG5503
`Notebook: Provision of substance
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`-- according to patent specification EP 0 693 475 B1
`and/or reaction specification for GB-Bu322-1-3
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`Salz = salt
`Materials
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`Class
`Reactants
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`Name
`Bu351, HBr-salt [LR]
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`Actual Amounts
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`Properties
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`Lot No.
`*
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`Equiv. Mass
`equiv.
`g
`5.00
`1.00
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`Volume Moles
`mL
`mmoles
`5.00
`15.81
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`Strength
`n/a
`3.16 M
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`n/a
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`n/a
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`n/a
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`n/a
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`n/a
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`n/a
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`150.00 100.00
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`871.32
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`8.71 M
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`n/a
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`n/a
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`n/a
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`11/90 M
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`132.50 100.00
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`1560.07 15.60 M
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`n/a
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`n/a
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`n/a
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`n/a
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`n/a
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`n/a
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`n/a
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`n/a
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`n/a
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`11.17 M
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`7.91 M
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`55.51M
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`0.64
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`2.60
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`2.60
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`10.09
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`100.00 wt/wt%
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`47-% hydrobromic acid, in water
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`Sodium hydrogen carbonate
`solution, saturated in water
`Dichloromethane, canned
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`Methylethylketone, canned
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`Trimethylchlorosilane
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`Water, deionized
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`Chemicals
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`Products
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`PG1026
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`Patent specification EP 0 693 475 B1:
`(+)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, hydrochloride (+21)
`
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`4.3 g (15 mmol) (+23) from Step 2 were mixed with 100 ml concentrated hydrobromic acid. Then the mixture
`was heated for 2 hours while refluxing. After cooling to room temperature, the reaction mixture was concentrated using a
`water stream vacuum. The residue was mixed with concentrated sodium hydrogen carbonate solution until alkaline. After
`extracting twice with 50 ml each dichloromethane, the combined organic phases were dried over sodium sulfate. Then
`dichloromethane was distilled off under vacuum and the residue (4 g) was taken up in 2-butanone. After adding
`trimethylchlorosilane/water, 3.8 g (98% of theoretical) of hydrochloride (+21) crystallized out.
`Melting point: 194 - 196 oC
`RT = +24.5 (c = 1.10, methanol)
`[α]D
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`November 12, 2009
`* 4.3g Bu351-HCl-salt correspond to 5.0 g Bu351-HBr salt
`Apparatus: 250-ml round flask, magnetic stirrer, oil bath, reflux cooler
`Execution:
`- preheat the oil bath to 130 oC
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`HIGHLY CONFIDENTIAL
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`GRT-NUC00074249_T
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`Page 7 of 10
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`Ruth Boggs, MA, CT
`ATA-Certified Translator (#62196) & Interpreter | Tel.: 703.378.9305 | rutheboggs@gmail.com
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`- mix Bu351, HBr-salt (5 g; 15.81 mmoles; 5.00 mL) with 47 %-hydrobromic acid in water (100 mL;
`871.32 mmoles; 100.00 mL)
`- reflux for 2 hours while stirring
`Workup:
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`Date:
`Date:
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`April 6, 2010
`April 24, 2010
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`Signature:
`Signature:
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`[signed]
`[signed]
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`HIGHLY CONFIDENTIAL
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`GRT-NUC00074249_T
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`Page 8 of 10
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`Ruth Boggs, MA, CT
`ATA-Certified Translator (#62196) & Interpreter | Tel.: 703.378.9305 | rutheboggs@gmail.com
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`CONFIDENTIAL
`[Grünenthal logo]
`Project: ________________________________ Lab journal No. ** 2186 **
`76
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`Page 2 of 2
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` -
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` remove the oil bath and allow to cool a bit
`- concentrate on the rotary evaporator
`- pour the residue into a 500 ml Erlenmeyer flask and slowly (Warning: severe
`development of gases) alkalize with saturated sodium hydrogen carbonate solution
`(pH9)
`- extract twice with a total of dichloromethane, canned product (100 mL; 1.56 moles;
`100.00 mL)
`- filter the organic extract over sodium sulfate; concentrate and dry under vacuum =
`2.603 g base
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`Hydrochloride precipitation:
`- take up 2.603 g base (corresponds to 11.75 mmol) in 17.5 ml MEK
`- add 0.235 ml water while stirring
`- add 1.49 ml (corresponds to 11.75 mmol) trimethylchlorosilane
`- stir another 90 minutes in the ice bath
`- filter off by suction; wash the solid again with MEK and suction dry = 2.60 g
`hydrochloride (cream-colored solid)
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`Powder diffractometry:
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`Theor. Yield: 4.08 g hydrochloride
`Yield:
`PG1026 (2.6 g; 10.09 mmoles; 2.60 g; 63.80 % yield)
`Appearance: cream-colored solid
`Fusion point: 199-201 oC
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`PG1026-001-1-1; hydrochloride: Polymorph B
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`April 6, 2010
`April 24, 2010
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`Signature:
`Signature:
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`[signed]
`[signed]
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`Date:
`Date:
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`HIGHLY CONFIDENTIAL
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`GRT-NUC00074250_T
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`Page 9 of 10
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`RUTH BOGGS, MA, CT
`ATA-Certified Translator (#62196) & Interpreter, English <> German
`_________________________________________________________________________________
`4111 Port Rae Lane • Fairfax, Virginia 22033 • Tel. (703) 378-9305 • FAX (703) 995-0767
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`CERTIFICATION
`
` hereby certify that
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`
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` I
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`I am a German into English and English into German translator, certified by the
`(1)
`American Translators Association;
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`I have translated and/or reviewed the translation of the following document(s)
`(2)
`from German into English:
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`
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`GRT-NUC00074243-250
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`The attached English translation is a true and correct translation of the German
`(3)
`language source document to the best of my knowledge and belief.
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`I declare that all statements made herein of my own knowledge are true, and all
`(4)
`statements made on information and belief are believed to be true. I understand that
`willful false statements and the like are punishable by fine or imprisonment, or both.
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`Date: February 26, 2015
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`________________________
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`Ruth Boggs, MA, CT
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`Page 10 of 10