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

HRID 254721Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 254721
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

Komponenten

6

Edukt 5

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

Produkt 1

HCID 66893167N-{(1S)-2-hydroxy-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}-2-methylpropane-2-sulfinamideAusbeute 61,6 %

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-8ee0ca49ee514dd1b8b73f4088f5dd58
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07875636B2

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