Acetic Acid → cis-N-[2-(cyclopropylmethyl-amino)-cyclohexyl]-2-methoxy-4,6-bis-trifluoromethyl-benzamide

HRID 659232

Reaction equation

HRID 659232 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:26])[C:10]1[C:15]([C:16]([F:19])([F:18])[F:17])=[CH:14][C:13]([C:20]([F:23])([F:22])[F:21])=[CH:12][C:11]=1[O:24][CH3:25].C(O)(=O)C.[CH:31]1([CH:34]=O)[CH2:33][CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH:31]1([CH2:34][NH:1][C@H:2]2[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]2[NH:8][C:9](=[O:26])[C:10]2[C:15]([C:16]([F:19])([F:18])[F:17])=[CH:14][C:13]([C:20]([F:21])([F:22])[F:23])=[CH:12][C:11]=2[O:24][CH3:25])[CH2:33][CH2:32]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58062915cis-N-(2-Amino-cyclohexyl)-2-methoxy-4,6-bis-trifluoromethyl-benzamide2×

Product 1

HCID 58062928cis-N-[2-(cyclopropylmethyl-amino)-cyclohexyl]-2-methoxy-4,6-bis-trifluoromethyl-benzamideYield 378.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

cis-N-(2-Amino-cyclohexyl)-2-methoxy-4,6-bis-trifluoromethyl-benzamide (intermediate H) (200 mg, 0.05 mmol) was dissolved in 10 mL methanol. Acetic acid (0.156 mg, 2.6 mmol) and cyclopropanecarboxaldehyde (73 mg, 1 mmol) were added and the reaction mixture was stirred 1 h at room temperature. Sodium triacetoxyborohydride (221 mg, 1 mmol) was added at 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. Crystallization with diisopropylether and a small amount of dichloromethane yielded cis-N-[2-(cyclopropylmethyl-amino)-cyclohexyl]-2-methoxy-4,6-bis-trifluoromethyl-benzamide as a white solid (83 mg, 36%), MS: m/e=439.3 [(M+H)+].

Workup

  1. stirringat stirring
  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. customCrystallization with diisopropylether

Sources & evidence

ORD record
ord-463b17ffe58f4b77b7149581e1b2703e
Source dataset
uspto-grants-2011_12
Patent number
US08080541B2

Linked notes

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