Trifluoroacetic acid → 2-methylpropyl[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]carbamate

HRID 1991252Notes

Reaction equation

HRID 1991252 reaction equation
[CH3:1][CH:2]([CH3:22])[CH2:3][O:4][C:5](=[O:21])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2(O)[CH2:18][CH2:17][S:16][CH2:15][CH2:14]2)=[C:9]([F:20])[CH:8]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>C(=O)([O-])[O-].[K+].[K+]>[CH3:1][CH:2]([CH3:22])[CH2:3][O:4][C:5](=[O:21])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:18][CH2:17][S:16][CH2:15][CH2:14]2)=[C:9]([F:20])[CH:8]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 98403602-methylpropyl [3-fluoro-4-(tetrahydro-4-hydroxy-2H-thiopyran-4-yl)phenyl]carbamate

Product 1

HCID 155500462-methylpropyl[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]carbamate

Reagents, catalysts & solvents 1

HCID 11430Potassium CarbonateSolvent

Procedure

A solution of 2-methylpropyl[3-fluoro-4-(tetrahydro-4-hydroxy-2H-thiopyran-4-yl)phenyl]carbamate (See Org. Proc. Res. Dev. 2001, 5, 80-83, 4.00 g, 12.2 mmol) in trifluoroacetic acid (19 mL, 244 mmol) under N2 is treated with triethylsilane (5.85 mL, 36.6 mmol) dropwise, stirred for 1 h, and then added dropwise to saturated aqueous potassium carbonate (250 mL) with vigorous stirring. The mixture is extracted with diethyl ether (200 mL), and the organic phase is washed with water (2×50 mL) and saline (50 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Trituration and filtration from diethyl ether/hexanes or ethyl acetate/hexanes gives the title compound, 1H NMR (CDCl3, 400 MHz) δ 7.26 (m, 1H), 7.11 (t, 1H), 6.97 (m, 1H), 6.59 (bs, 1H), 3.95 (d, 2H), 2.85 (m, 3H), 2.68 (m, 2H), 2.09 (m, 2H), 1.98 (m, 1H), 1.84 (m, 2H), 0.96 (d, 6H).

Workup

  1. extractionThe mixture is extracted with diethyl ether (200 mL)
  2. washthe organic phase is washed with water (2×50 mL) and saline (50 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. filtrationTrituration and filtration from diethyl ether/hexanes or ethyl acetate/hexanes

Sources & evidence

ORD record
ord-344864edf5474693a6bb86f9231de5db
Source dataset
uspto-grants-2010_01
Patent number
US07645781B2

Reaction notes

Loading…