Phenylglyoxylic Acid → N-(3,4-Dimethyl-phenyl)-2-oxo-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamide

HRID 1094356Notes

Reaction equation

HRID 1094356 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][CH2:11][C:12]2[CH:13]=[N:14][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:17]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].[C:22]([C:30](O)=[O:31])(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.CC(OC)(C)C>[CH3:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:10][CH2:11][C:12]2[CH:13]=[N:14][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:17]=2)[C:30](=[O:31])[C:22](=[O:29])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

7

Reactant 4

HCID 11915Phenylglyoxylic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 58007591(3,4-Dimethyl-phenyl)-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amine

Product 1

HCID 44546313N-(3,4-Dimethyl-phenyl)-2-oxo-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamideYield 53.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of (3,4-dimethyl-phenyl)-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amine (172 mg, 0.58 mmol) in DMF (4 mL) was added under a nitrogen atmosphere at 0° C. benzoylformic acid (105 mg, 0.70 mmol), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (280 mg, 0.88 mmol) and N,N-diisopropyl ethyl amine (299 μl, 1.75 mmol). The resulting solution was stirred for 18 h at ambient temperature. It was diluted with TBME (15 mL) and washed with aqueous hydrochloric acid (1 M, 15 mL), water (15 mL), aqueous Na2CO3 (saturatedm, 15 mL) and brine (15 mL). The combined aqueous layers were extracted with TBME (15 mL) and the combined organic layers dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 60:40) afforded the title compound (132 mg, 53%) as a light brown oil. MS m/e: 427.2 [M+H]+.

Workup

  1. washwashed with aqueous hydrochloric acid (1 M, 15 mL), water (15 mL), aqueous Na2CO3 (saturatedm, 15 mL) and brine (15 mL)
  2. extractionThe combined aqueous layers were extracted with TBME (15 mL)
  3. dry with materialthe combined organic layers dried over sodium sulfate
  4. concentrationConcentration and purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 60:40)

Sources & evidence

ORD record
ord-c68051d5810644b68928a3c5efb7d540
Source dataset
uspto-grants-2012_03
Patent number
US08133909B2

Reaction notes

Loading…