Ethyl Acetate → (R)-N-{2-Chloro-4-([5-ethoxycarbonyl-3-pyridyl]sulphanyl)phenyl}-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 2301029Notes

Reaction equation

HRID 2301029 reaction equation
[F-].[Cs+].[Cl:3][C:4]1[CH:9]=[C:8]([S:10][Si](C(C)C)(C(C)C)C(C)C)[CH:7]=[CH:6][C:5]=1[NH:21][C:22](=[O:30])[C@:23]([OH:29])([CH3:28])[C:24]([F:27])([F:26])[F:25].Br[C:32]1[CH:33]=[N:34][CH:35]=[C:36]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:37]=1.C(OCC)(=O)C>CC(N(C)C)=O.[Cl-].[Na+].O.[Cu]Cl>[Cl:3][C:4]1[CH:9]=[C:8]([S:10][C:32]2[CH:33]=[N:34][CH:35]=[C:36]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:37]=2)[CH:7]=[CH:6][C:5]=1[NH:21][C:22](=[O:30])[C@:23]([OH:29])([CH3:28])[C:24]([F:25])([F:26])[F:27]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 25953Cesium fluorideHCID 140785Ethyl 5-bromopyridine-3-carboxylateHCID 69748868(R)-N-(2-Chloro4-(triisopropylsilylsulphanyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

Product 1

HCID 69751310(R)-N-{2-Chloro-4-([5-ethoxycarbonyl-3-pyridyl]sulphanyl)phenyl}-2-hydroxy-2-methyl-3,3,3-trifluoropropanamideYield 53%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 31374DimethylacetamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
155 °C

Procedure

Caesium fluoride (0.26 g) was added to a solution of (R)-N-(2-chloro-4-(triisopropylsilylsulphanyl)phenyl]-2-hydroxy-2-methyl-3,3,3 trifluoropropanamide (0.74 g) (Method 28) in anhydrous DMA (5 ml) under argon and the mixture was stirred for 17 hours. Copper(I) chloride (0.17 g) followed by 3-bromo-5-carboethoxypyridine (0.37 g) were added and the mixture was heated to 155° C. for 4 hours and allowed to cool to ambient temperature. Ethyl acetate (20 ml) and brine (20 ml) were added and the mixture was filtered through a pad of diatomaceous earth which was washed with ethyl acetate (3×50 ml). The filtrates were combined, washed with brine (3×50 ml) and then dried. Volatile material was removed by evaporation and the residue was purified on a silica gel Mega Bond Elut column eluting with 10-40% ethyl acetate/iso-hexane to give the title compound (in 53% yield) as a foam. NMR (CDCl3): 1.39 (t, 3H), 1,57 (s, 3H), 4.00 (s, 1H), 4.40 (q, 2H), 7.34-7.37 (m, 1H), 7.46 (d, 1H), 8.18 (s, 1H), 8.42 (d, 1H), 8.62 (s, 1H), 9.03 (s, 1H), 9.04 (s, 1H); MS (ESP−): 447.

Workup

  1. additionwere added
  2. temperatureto cool to ambient temperature
  3. filtrationthe mixture was filtered through a pad of diatomaceous earth which
  4. washwas washed with ethyl acetate (3×50 ml)
  5. washwashed with brine (3×50 ml)
  6. customdried
  7. customVolatile material was removed by evaporation
  8. customthe residue was purified on a silica gel Mega Bond Elut column
  9. washeluting with 10-40% ethyl acetate/iso-hexane

Sources & evidence

ORD record
ord-3ea6224cb15944b89e99a9d296d359cd
Source dataset
uspto-grants-2002_12
Patent number
US06498275B1

Reaction notes

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