Water → HCID 68682193, compound

HRID 1865466Notes

Reaction equation

HRID 1865466 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-5894bc9dd3b84106b15e39b0ef652351
Source dataset
uspto-grants-2009_12
Patent number
US07626056B2

Reaction notes

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