Water → HCID 68682193, compound

HRID 2263609Notes

Reaction equation

HRID 2263609 reaction equation
Cl[C:2]1[N:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:3]=1[C:4]([NH:6][CH2:7][C:8]1([CH2:21][CH:22]2[CH2:24][CH2:23]2)[CH2:13][CH2:12][CH:11]([S:14]([CH2:17][CH:18]2[CH2:20][CH2:19]2)(=[O:16])=[O:15])[CH2:10][CH2:9]1)=[O:5].[CH3:33][O-:34].[Na+].O>CO>[CH:18]1([CH2:17][S:14]([CH:11]2[CH2:12][CH2:13][C:8]([CH2:7][NH:6][C:4](=[O:5])[C:3]3[CH:25]=[CH:26][C:27]([C:29]([F:32])([F:31])[F:30])=[N:28][C:2]=3[O:34][CH3:33])([CH2:21][CH:22]3[CH2:24][CH2:23]3)[CH2:9][CH2:10]2)(=[O:16])=[O:15])[CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 962WaterHCID 10942334Sodium MethoxideHCID 86609534HCID 86609534, compound

Product 1

HCID 68682193HCID 68682193, compoundYield 96.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-chloro-N-(4-cyclopropylmethanesulfonyl-1-cyclopropylmethylcyclohexylmethyl)-6-trifluoromethylnicotinamide (50 mg, 0.10 mmol) in methanol (5 ml) was treated with sodium methoxide (11 mg, 0.20 mmol) and the mixture was allowed to stir at ambient temperature for 1 hour then heated under reflux for 4 hours. Water (1 ml) was added and the solvent evaporated. The residue was partitioned between dichloromethane (5 ml) and water (5 ml) and the layers separated using a 5 micron PTFE frit and the filtrate was evaporated. The residue was purified by preparative plate chromatography on silica eluting with 10% ethyl acetate in dichloromethane. Collecting the appropriate band followed by trituration of the silica with ethyl acetate, filtration and evaporation gave a colourless oil (47 mg, 95%). 1H NMR δ (ppm) (CDCl3): 8.67 (1H, d, J=7.6 Hz), 7.92 (1H, s), 7.44 (1H, d, J=7.6 Hz), 4.15 (3H, s), 3.65 (2H, d, J=6.1 Hz), 2.94-2.89 (3H, m), 2.07-1.84 (6H, m), 1.40-1.32 (2H, m), 1.25-1.15 (3H, m), 0.78-0.70 (3H, m), 0.57-0.53 (2H, m), 0.42 (2H, q, J=5.3 Hz), 0.07 (2H, q, J=5.0 Hz). MS (m/e)=489.

Workup

  1. temperaturethen heated
  2. temperatureunder reflux for 4 hours
  3. customthe solvent evaporated
  4. customThe residue was partitioned between dichloromethane (5 ml) and water (5 ml)
  5. customthe layers separated
  6. customthe filtrate was evaporated
  7. customThe residue was purified by preparative plate chromatography on silica eluting with 10% ethyl acetate in dichloromethane
  8. customCollecting the appropriate band
  9. filtrationfollowed by trituration of the silica with ethyl acetate, filtration and evaporation

Sources & evidence

ORD record
ord-7642f9acdad6434f8c1456e2175f3a8d
Source dataset
uspto-grants-2010_12
Patent number
US07851638B2

Reaction notes

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