(3S,4S)-3-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-4-[(R)-1-phenyl-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester → (3S,4S)-3-amino-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1169257Notes

Reaction equation

HRID 1169257 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([NH:13][C@@H](C2C=CC=CC=2)C)[C@@H:10]([CH2:22][N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[CH2:24]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>[OH-].[Pd+2].[OH-].CO>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@H:10]([CH2:22][N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[CH2:24]2)[C@H:11]([NH2:13])[CH2:12]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 69748103(3S,4S)-3-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-4-[(R)-1-phenyl-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69747056(3S,4S)-3-amino-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 95.3%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

(3S, 4S)-3-[(S)-3-(4-Fluorobenzyl)-piperidin-1-ylmethyl]-4-[(R)-1-phenyl-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (100 mg, 0.201 mmol), palladium hydroxide (20 weight % on carbon, dry basis; 40 mg) and methanol (7 mL) were combined in a pressure bottle and shaken under hydrogen atmosphere (50-55 psig) for 20 h . The mixture was filtered through Celite, and the solids were rinsed with ethanol. The filtrate was concentrated to give the product as a glassy foam (75 mg, 95%), used without further purification. 1H NMR (300 mHz, CD3OD) δ7.20 (m, 2H), 6.98 (m, 2H), 3.18-2.42 (15H), 1.80-1.50 (4H), 1.41 (s, 9H); mass spec. (ES+) m/z 392.4.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. washthe solids were rinsed with ethanol
  3. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-7e0f3459936f4689918b5a650f22ae45
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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