Acetic Acid → 4-(Trifluoromethyl)benzamide

HRID 659229

Reaction equation

HRID 659229 reaction equation
CO[C:3]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15](SC)[C:4]=1[C:5]([NH:7]C1CCCCC1=O)=[O:6].C(O)(=O)C.N1CCCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[F:20][C:19]([F:21])([F:22])[C:17]1[CH:18]=[CH:3][C:4]([C:5]([NH2:7])=[O:6])=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 580629692-methoxy-6-methylsulfanyl-N-(2-oxo-cyclohexyl)-4-trifluoromethyl-benzamide2×

Product 1

HCID 746844-(Trifluoromethyl)benzamideYield 62.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Methoxy-6-methylsulfanyl-N-(2-oxo-cyclohexyl)-4-trifluoromethyl-benzamide (intermediate B, 380 mg, 1.05 mmol) was dissolved in 10 mL tetrahydrofurane. Acetic acid (145 mg, 2.4 mmol) and pyrrolidine (97 mg, 1.4 mmol) were added and the reaction mixture was stirred 1 h at room temperature. Sodium triacetoxyborohydride (290 mg, 1.4 mmol) was added and stirring was continued at room temperature overnight. The mixture was extracted with 2N sodium carbonate solution and ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0→140:10:1) yielded cis-2-methoxy-6-methylsulfanyl-N-2-pyrrolidin-1-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow solid (125 mg, 28%), MS: m/e=417.3 [(M+H)+] and trans-2-methoxy-6-methylsulfanyl-N-2-pyrrolidin-1-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow solid (28 mg, 6%), MS: m/e=417.3 [(M+H)+].

Workup

  1. stirringstirring
  2. waitwas continued at room temperature overnight
  3. extractionThe mixture was extracted with 2N sodium carbonate solution and ethyl acetate
  4. customThe combined organic phases were dried on sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0→140:10:1)

Sources & evidence

ORD record
ord-d2e99e10e4a748b2982262634b7d0862
Source dataset
uspto-grants-2011_12
Patent number
US08080541B2

Linked notes

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