Methanol → N-{(1S)-2-hydroxy-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}-2-methylpropane-2-sulfinamide

HRID 254721노트

반응식

HRID 254721 반응식
O=[O+][O-].[CH3:4][C:5]([S@:8]([N:10]=[CH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[CH:14][N:13]=1)=[O:9])([CH3:7])[CH3:6].ClCCl.[BH4-].[Na+].[CH3:29][OH:30]>>[OH:30][CH2:29][C@@H:11]([NH:10][S:8]([C:5]([CH3:4])([CH3:6])[CH3:7])=[O:9])[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]([F:23])([F:21])[F:22])=[CH:14][N:13]=1

참가 물질

6

반응물 5

HCID 887MethanolHCID 6344DichloromethaneHCID 24823OzoneHCID 4311764Sodium borohydrideHCID 66893280(R)-2-methyl-N-[(5-(2,2,2-trifluoroethoxy)pyridine-2-yl)methylene]propane-2-sulfinamide

생성물 1

HCID 66893167N-{(1S)-2-hydroxy-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}-2-methylpropane-2-sulfinamide수율 61.6%

실험 절차

Ozone was bubbled through a mixture of (R)-2-methyl-N-[(5-(2,2,2-trifluoroethoxy)pyridine-2-yl)methylene]propane-2-sulfinamide (8.10 g, 24.1 mmol) in a 1:1 mixture of dichloromethane and methanol (96 ml) at −78° C. until no starting material was observed by LC/MS. Nitrogen was bubbled through the reaction for fifteen minutes. To the solution was added in portions sodium borohydride (3.64 g, 96.0 mmol) over ten minutes. The reaction was allowed to warm to room temperature, stirred for 16 hours and then concentrated in vacuum. The resulting residue was washed with brine (2×60 ml) and extracted with ethyl acetate (2×75 ml). The organic extracts were combined, dried over Na2SO4, filtered and concentrated to give an oil. Purification by flash chromatography (SiO2, 50-100% ethyl acetate in hexanes, followed by 0-10% methanol in ethyl acetate, gradient) gave N-{(1S)-2-hydroxy-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}-2-methylpropane-2-sulfinamide as a white solid (5.10 g, 61.6%); 1H NMR (400 MHz, CDCl3) δ 8.28 (d, J=2.8 Hz, 1H), 7.42 (d, J=8.4 Hz, 1H), 7.28 (dd, J=2.8 Hz and 8.4 Hz, 1H), 4.62-4.60 (m, 1H), 4.53-4.48 (m, 1H), 4.39 (q, J=8.0 Hz, 2H), 3.91-3.88 (m, 2H), 3.22 (m, 1H), 1.27 (s, 9H); MS (Electrospray): m/z 341.1 (M+H).

후처리

  1. customNitrogen was bubbled through the reaction for fifteen minutes
  2. concentrationconcentrated in vacuum
  3. washThe resulting residue was washed with brine (2×60 ml)
  4. extractionextracted with ethyl acetate (2×75 ml)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give an oil
  9. customPurification by flash chromatography (SiO2, 50-100% ethyl acetate in hexanes, followed by 0-10% methanol in ethyl acetate, gradient)

출처 및 근거

ORD 기록
ord-8ee0ca49ee514dd1b8b73f4088f5dd58
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07875636B2

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