Formic Acid → (R)-3-[[N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl]amino]pyrrolidine

HRID 133560

Reaction equation

HRID 133560 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][C@@H:18]1[CH2:22][CH2:21][N:20](CC2C=CC(Cl)=CC=2)[CH2:19]1)=[O:16])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)=O>[OH-].[OH-].[Pd+2].CO>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:36])[F:37])=[CH:31][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][C@@H:18]1[CH2:22][CH2:21][NH:20][CH2:19]1)=[O:16])=[O:12])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 284Formic AcidHCID 54203221(R)-3-[[N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl]amino]-1-(4-chlorobenzyl)pyrrolidine

Product 1

HCID 54307129(R)-3-[[N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl]amino]pyrrolidine

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of (R)-3-[[N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl]amino]-1-(4-chlorobenzyl)pyrrolidine (6.3 g, 11.4 mmol) with Pd(OH)2 (1.68 g), formic acid (3.7 mL) and methanol (80 mL) was stirred at 50° C. overnight. The mixture was cooled to room temperature, and the palladium catalyst was then removed by filtration through Celite. The resulting filtrate was concentrated and purified by column chromatography [SiO2, ethyl acetate/methanol=(5:1) to (4:1)] to thereby provide (R)-3-[[N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl]amino]pyrrolidine (4.42 g, 90%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 1.48 (s, 9H), 2.0-2.4 (m, 2H), 3.42-3.71 (m, 5H), 4.00-4.22 (m, 2H), 4.56 (br, 1H), 7.48 (d, J=9.0 Hz, 1H), 7.93 (s, 1H), 8.17 (br, 1H), 8.33 (d, J=9.0 Hz, 1H), 8.45 (br, 1H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customthe palladium catalyst was then removed by filtration through Celite
  3. concentrationThe resulting filtrate was concentrated
  4. custompurified by column chromatography [SiO2, ethyl acetate/methanol=(5:1) to (4:1)] to thereby provide (R)-3-[[N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl]amino]pyrrolidine (4.42 g, 90%) as a white solid

Sources & evidence

ORD record
ord-34382c61fea44e9f981f766d1eb53c37
Source dataset
uspto-grants-2008_06
Patent number
US07390830B1

Linked notes

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