[1,1-Dioxo-(3R,4S)-4-[(R)-1-phenyl-ethylamino]-tetrahydrothiophen-3-yl]-[(S)-3-(4-fluoro-benzyl)-piperidin-1-yl]-methanone → [(3R,4S)-4-Amino-1,1-dioxo-tetrahydrothiophen-3-yl]-[(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-methanone

HRID 1169248Notes

Reaction equation

HRID 1169248 reaction equation
[O:1]=[S:2]1(=[O:32])[CH2:6][C@@H:5]([NH:7][C@@H](C2C=CC=CC=2)C)[C@H:4]([C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH2:19]2)=[O:17])[CH2:3]1>[OH-].[Pd+2].[OH-].CO>[NH2:7][C@@H:5]1[CH2:6][S:2](=[O:1])(=[O:32])[CH2:3][C@H:4]1[C:16]([N:18]1[CH2:23][CH2:22][CH2:21][C@@H:20]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[CH2:19]1)=[O:17]

Participants

4

Reactant 1

HCID 69747758[1,1-Dioxo-(3R,4S)-4-[(R)-1-phenyl-ethylamino]-tetrahydrothiophen-3-yl]-[(S)-3-(4-fluoro-benzyl)-piperidin-1-yl]-methanone

Product 1

HCID 69748830[(3R,4S)-4-Amino-1,1-dioxo-tetrahydrothiophen-3-yl]-[(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-methanoneYield 108.3%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

[1,1-Dioxo-(3R,4S)-4-[(R)-1-phenyl-ethylamino]-tetrahydrothiophen-3-yl]-[(S)-3-(4-fluoro-benzyl)-piperidin-1-yl]-methanone (790 mg, 1.72 mmol), palladium hydroxide (20 weight % on carbon, dry basis; 1.1 g) and methanol (50 mL) were combined in a pressure bottle and shaken under a hydrogen atmosphere (55-60 psig) for 20.5 h. The mixture was filtered through Celite, and the solids were washed thoroughly with methanol. The filtrate was concentrated to give the product as a solid (660 mg, quantitative), used without further purification. 1H NMR (300 mHz, CD3OD) δ7.20 (m, 2H), 7.00 (m, 2H), 4.45 and 4.32 (2m, 1H), 4.09 (m, 1H), 3.90 and 3.79 (2m, 1H), 3.7-3.4 (m, 2H), 3.13 (m, 2H), 2.87 and 2.69 (2m, 1H), 2.56 (m, 2H), 1.79 (m, 3H), 1.28 (m, 3H), 0.88 (m, 1H), ESI MS: (M+H)+=355.2.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. washthe solids were washed thoroughly with methanol
  3. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-cd45d916aee447f5ab6b3ada470e2564
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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