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

HRID 2383543ノート

反応式

HRID 2383543 の反応式
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

参加物

6

反応物 5

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

生成物 1

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

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-c464ba21b8484a908412bd0d8298c6d1
出典データセット
uspto-grants-2012_09
特許番号
US08263627B2

反応ノート

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