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

HRID 1169247Notes

Reaction equation

HRID 1169247 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C@@H:7]2[CH2:12][CH2:11][CH2:10][N:9]([C:13]([C@H:15]3[C@H:19]([NH:20][C@@H:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH3:22])[CH2:18]S[CH2:16]3)=[O:14])[CH2:8]2)=[CH:4][CH:3]=1.CC(C)=O.O.[S:36]([O-:41])(O[O-])(=O)=[O:37].[K+].[K+]>CO>[O:37]=[S:36]1(=[O:41])[CH2:18][C@@H:19]([NH:20][C@@H:21]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH3:22])[C@H:15]([C:13]([N:9]2[CH2:10][CH2:11][CH2:12][C@@H:7]([CH2:6][C:5]3[CH:29]=[CH:30][C:2]([F:1])=[CH:3][CH:4]=3)[CH2:8]2)=[O:14])[CH2:16]1

Participants

6

Reactant 4

HCID 180AcetoneHCID 962WaterHCID 10313463Potassium peroxymonosulphateHCID 69747757[(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-[(3R,4S)-4-((R)-1-phenyl-ethylamino)-tetrahydrothiophen-3-yl]-methanone

Product 1

HCID 69747758[1,1-Dioxo-(3R,4S)-4-[(R)-1-phenyl-ethylamino]-tetrahydrothiophen-3-yl]-[(S)-3-(4-fluoro-benzyl)-piperidin-1-yl]-methanoneYield 72.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

[(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-[(3R,4S)-4-[(R)-1-phenyl-ethylamino]-tetrahydro-thiophen-3-yl]-methanone (1.02 g, 2.39 mmol) was dissolved in methanol (10 mL) and acetone (10 mL) and stirred on ice. Water (10 mL) was added, and the resulting heterogeneous mixture was treated with potassium peroxymonosulfate (Oxone®, 3.67 g, 5.98 mmol). After 5 min the cooling bath was removed and the mixture was stirred at room temperature. After 20.5 h , the mixture was concentrated and diluted with water. The pH was adjusted to ca. 11 with 1N sodium hydroxide, and the mixture was extracted with ethyl acetate. The combined extracts were dried (Na2SO4) and concentrated, and the residue was purified by flash column chromatography (2.5% 2-propanol/chloroform) to provide the product as a glass (790 mg, 72%). 1H NMR (300 mHz, CDCl3) δ7.31 (m, 5H), 7.11 (m, 2H), 7.06 (m, 2H), 4.50 (m, 1H), 4.0-3.7 (m, 3H), 3.5-2.9 (m, 5H), 2.7-2.5 (m, 4H), 1.9-1.6 (m, 4H), 1.43 (m, 1H), 1.33 (m, 3H), 1.20 (m, 1H), ESI MS: (M+H)+=459.3.

Workup

  1. customAfter 5 min the cooling bath was removed
  2. concentrationthe mixture was concentrated
  3. additiondiluted with water
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe combined extracts were dried (Na2SO4)
  6. concentrationconcentrated
  7. customthe residue was purified by flash column chromatography (2.5% 2-propanol/chloroform)

Sources & evidence

ORD record
ord-ad4c37000c024bc192bcf1ac5d104488
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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