3-Carboxybenzaldehyde → 3-Formyl-N-{[4-(trifluoromethoxy)phenyl]methyl}benzamide

HRID 1696611Notes

Reaction equation

HRID 1696611 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=[O:8])([OH:3])=O.[F:12][C:13]([F:24])([F:23])[O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][CH:16]=1.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C>C(Cl)Cl>[CH:7]([C:6]1[CH:5]=[C:4]([CH:11]=[CH:10][CH:9]=1)[C:1]([NH:20][CH2:19][C:18]1[CH:21]=[CH:22][C:15]([O:14][C:13]([F:12])([F:23])[F:24])=[CH:16][CH:17]=1)=[O:3])=[O:8]

Participants

6

Reactant 4

HCID 120773-CarboxybenzaldehydeHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 5718464-(Trifluoromethoxy)benzylamine

Product 1

HCID 714239883-Formyl-N-{[4-(trifluoromethoxy)phenyl]methyl}benzamideYield 103.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

to a solution of 300 mg of 3-carboxybenzaldehyde (2 mmoles) and 382 mg of 4-(trifluoromethoxy)benzylamine (2 mmoles) in 5 ml of DCM is successively added 540 mg of 1-hydroxybenzotriazole (HOBt) (4 mmoles) and 0.63 mg of diisopropylcarbodiimide (DIC) (4 mmoles). The reaction mixture is stirred overnight at room temperature and then poured into 20 ml of 10% KH2SO4 solution. The mixture is extracted twice with 15 ml of ethyl acetate. The combined organic extracts are washed with 20 ml of water and 20 ml of brine, dried over MgSO4 and concentrated giving 670 mg of 3-formyl-N-(4-trifluoromethoxy-benzyl)-benzamide (yield=85%). Analytical LC/MS method A: ([M+H]+): 324, RT: 5.24 min (gradient 5 to 85% acetonitrile in 7 min). Compound 60 is prepared as described for example 2 starting with 21.3 mg of of N-Boc-3,5-diketopiperidine (0.1 mmole), 8.3 mg 3-aminopyrazole (0.1 mmole) and 32.3 mg of 3-formyl-N-(4-trifluoromethoxy-benzyl)-benzamide (0.1 mmole) in a mixture of 0.5 ml of ethanol and 0.5 ml of DMF, resulting in 22.5 mg of product 60 after purification by preparative LC/MS. (method A, yield=38%). Analytical LC/MS method A: ([M+H]+): 484, RT: 2.51 min (gradient 2 to 80% acetonitrile in 7 min).

Workup

  1. extractionThe mixture is extracted twice with 15 ml of ethyl acetate
  2. washThe combined organic extracts are washed with 20 ml of water and 20 ml of brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-4467bb72f915480393baeeb41244dd73
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

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