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

HRID 1062403Notes

Reaction equation

HRID 1062403 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
1 °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 1° 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 was 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 was 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-6c80b4b7223141ea87c22e124e661ae5
Source dataset
uspto-grants-2005_11
Patent number
US06960688B2

Reaction notes

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