Dimethylformamide → HCID 69825004, compound

HRID 2120363Notes

Reaction equation

HRID 2120363 reaction equation
C([Si](C(C)C)(C(C)C)[SH:5])(C)C.[H-].[Na+].I[C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:30])[C@:23]([OH:29])([CH3:28])[C:24]([F:27])([F:26])[F:25])=[C:17]([Cl:31])[C:16]=1[Cl:32].CN(C=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.CCOC(C)=O>[Cl:31][C:17]1[C:16]([Cl:32])=[C:15]([SH:5])[CH:20]=[CH:19][C:18]=1[NH:21][C:22](=[O:30])[C@:23]([OH:29])([CH3:28])[C:24]([F:27])([F:26])[F:25]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 3435097Tris(propan-2-yl)silanethiolHCID 69824119HCID 69824119, compound

Product 1

HCID 69825004HCID 69825004, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Triisopropylsilane thiol (2.0 ml) was added to a stirred suspension of sodium hydride (0.37 g, 60% mineral oil dispersion) in anhydrous THF (30 ml) cooled to 0° C. under argon. After 20 minutes at this temperature the reaction mixture was added to a stirred suspension of (R)-N-[4-iodo-2,3-dichlorophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Method 4) (4.0 g) and tetrakis(triphenylphosphine)palladium(0) (0.86 g) in anhydrous toluene (40 ml). The mixture was heated to 85° C. for 5 hours and DMF (10 ml) was added to obtain a clear solution. Heating was continued for a further 17 hours. The mixture was allowed to cool to ambient temperature, EtOAc (200 ml) was added and the mixture washed with brine (3×100 ml) and dried. Volatile material was removed by evaporation and the residue was purified by flash chromatography eluting with 1-50% EtOAc/isohexane to give the title compound (0.448 g) as an orange solid. NMR: 1.58 (s, 3H), 7.55 (d, 1H), 7.66 (d, 1H), 7.73 (s, 1H), 9.80 (s, 1H); m/z: 332.

Workup

  1. temperatureThe mixture was heated to 85° C. for 5 hours
  2. customto obtain a clear solution
  3. temperatureHeating
  4. temperatureto cool to ambient temperature
  5. washthe mixture washed with brine (3×100 ml)
  6. customdried
  7. customVolatile material was removed by evaporation
  8. customthe residue was purified by flash chromatography
  9. washeluting with 1-50% EtOAc/isohexane

Sources & evidence

ORD record
ord-7175af922d844422b76f211ebd210fc9
Source dataset
uspto-grants-2004_02
Patent number
US06689909B1

Reaction notes

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