Benzenamine, 3,5-bis(trifluoromethyl)- → HCID 86652393, compound

HRID 2068265Notes

Reaction equation

HRID 2068265 reaction equation
[Li]CCCC.[F:6][C:7]([F:20])([F:19])[C:8]1[CH:9]=[C:10]([CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1)[NH2:11].C[O:22][C:23]([C:25]1([CH2:39]OS(C)(=O)=O)[CH2:29][C:28](=[O:30])[N:27]([C:31]2[C:36]([CH3:37])=[CH:35][CH:34]=[CH:33][C:32]=2[CH3:38])[CH2:26]1)=O>C1COCC1>[F:6][C:7]([F:19])([F:20])[C:8]1[CH:9]=[C:10]([NH:11][C:23]([C:25]23[CH2:39][CH:29]2[C:28](=[O:30])[N:27]([C:31]2[C:32]([CH3:38])=[CH:33][CH:34]=[CH:35][C:36]=2[CH3:37])[CH2:26]3)=[O:22])[CH:12]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:14]=1

Participants

5

Reactant 3

HCID 9480Benzenamine, 3,5-bis(trifluoromethyl)-HCID 86652394HCID 86652394, compoundHCID 178418339Butyllithium

Product 1

HCID 86652393HCID 86652393, compoundYield 10.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

n-BuLi (2.5 M solution in hexanes, 560 μL, 1.39 mmol) was added to a solution of 3,5-bis-trifluoromethylaniline (216.5 μL, 0.545 mmol) in THF (3 mL) at room temperature. The resulting dark brown colored solution was stirred for 10 min at room temperature. A solution of 1-(2,6-dimethyl-phenyl)-3-methanesulfonyloxymethyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (prepared from step b, 165 mg, 0.465 mmol) in THF (2 mL) was added and stirred for 2 h at 75° C. The reaction mixture was then purified by preparative HPLC (15→85% gradient of MeCN—H2O with 0.1% TFA). The pure fractions were lyophilized to afford 3-(2,6-dimethyl-phenyl)-4-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide (22 mg, 10% yield). LC-MS: Rt (retention time): 2.98 min, MS: (ES) m/z 457.2 (M+H+). 1H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 8.32 (s, 2H), 7.78 (s, 1H), 7.02-7.18 (m, 3H), 4.18 (d, 1H, J=9.7 Hz), 3.68 (d, 1H, J=9.7 Hz), 2.68-2.75 (m, 1H), 2.18 (s, 3H), 2.08-2.12 (m, 1H), 2.05 (s, 3H), 1.45 (t, 1H, J=3.9 Hz).

Workup

  1. stirringstirred for 2 h at 75° C
  2. customThe reaction mixture was then purified by preparative HPLC (15→85% gradient of MeCN—H2O with 0.1% TFA)

Sources & evidence

ORD record
ord-1a7d182d94d94f77b7cbd0de1db63bdf
Source dataset
uspto-grants-2012_10
Patent number
US08293925B2

Reaction notes

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