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

HRID 2383543Notes

Reaction equation

HRID 2383543 reaction equation
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

Participants

6

Reactant 5

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

Product 1

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

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-c464ba21b8484a908412bd0d8298c6d1
Source dataset
uspto-grants-2012_09
Patent number
US08263627B2

Reaction notes

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