Ethyl Acetate → (R)-N-(2-Chloro4-(triisopropylsilylsulphanyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 2301059Notes

Reaction equation

HRID 2301059 reaction equation
[CH:1]([Si:4]([CH:9]([CH3:11])[CH3:10])([CH:6]([CH3:8])[CH3:7])[SH:5])([CH3:3])[CH3:2].[H-].[Na+].[Cl:14][C:15]1[CH:20]=[C:19](I)[CH:18]=[CH:17][C:16]=1[NH:22][C:23](=[O:31])[C@:24]([OH:30])([CH3:29])[C:25]([F:28])([F:27])[F:26].C(OCC)(=O)C>C1COCC1.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:14][C:15]1[CH:20]=[C:19]([S:5][Si:4]([CH:1]([CH3:3])[CH3:2])([CH:6]([CH3:8])[CH3:7])[CH:9]([CH3:11])[CH3:10])[CH:18]=[CH:17][C:16]=1[NH:22][C:23](=[O:31])[C@:24]([OH:30])([CH3:29])[C:25]([F:26])([F:28])[F:27]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 3435097Tris(propan-2-yl)silanethiolHCID 54268602(R)-N-(2-chloro4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

Product 1

HCID 69748868(R)-N-(2-Chloro4-(triisopropylsilylsulphanyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Triisopropylsilanethiol (2.8 ml) was added to a stirred suspension of sodium hydride (60% mineral oil dispersion, 0.53 g) in anhydrous THF (40 ml) cooled to 0° C. under argon. After 15 minutes at this temperature tetrakis(triphenylphosphine)palladium(0) (1.21 g) was added and this solution was added to (R)-N-(2-chloro-4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 197) (5.2 g) in anhydrous toluene (40 ml) and the mixture was heated to 85° C. for 2 hours. The mixture was allowed to cool to ambient temperature. ethyl acetate (200 ml) was added and the mixture as washed with brine (100 ml) and dried. Volatile material was removed by evaporation and the residue was purified on a silica gel flash column eluting with 1-20% ethyl acetate/hexane to give the title compound (6.51 g) as a gum. NMR (CDCl3) 1.07-1.1 (d, 18H), 1.20-1.28 (m, 3H), 1.74 (s, 3H), 3.64 (s, 1H), 7.39-7.42 (m, 1H), 7.53 (s, 1H), 8.23 (d, 1H), 8.81 (s, 1H); MS (ESP−): 454.

Workup

  1. temperaturethe mixture was heated to 85° C. for 2 hours
  2. temperatureto cool to ambient temperature
  3. washthe mixture as washed with brine (100 ml)
  4. customdried
  5. customVolatile material was removed by evaporation
  6. customthe residue was purified on a silica gel flash column
  7. washeluting with 1-20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-9dd4cbe059754af19d43c19a276b95bb
Source dataset
uspto-grants-2002_12
Patent number
US06498275B1

Reaction notes

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