3,5-Bis(trifluoromethyl)benzoyl chloride → HCID 86670829, compound
Reaction equation
[CH3:1][NH:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[F:25][C:26]([F:41])([F:40])[C:27]1[CH:28]=[C:29]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[C:30](Cl)=[O:31]>C1COCC1>[CH3:1][N:2]([C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:30](=[O:31])[C:29]1[CH:33]=[C:34]([C:36]([F:37])([F:38])[F:39])[CH:35]=[C:27]([C:26]([F:25])([F:40])[F:41])[CH:28]=1Participants
Conditions
- Temperature
- -78 °C
Procedure
To a solution of methyl-(4-phenyl-pyridin-3-yl)-amine (160 mg, 0.87 mmol) in THF (4 mL) under nitrogen was added LiHMDS (1.3 mL, 1.3 mmol, 1M solution in THF) at −78° C. and the resulting reaction mixture was stirred for 30 min at −78° C. Then 3,5-bis(trifluoromethyl)-benzoyl chloride (480 mg, 1.74 mmol, CAS RN 1271-19-8) in THF (1 mL) was added to the reaction mixture at −78° C. and the reaction mixture was stirred for another 12 hours at 25° C. The reaction mixture was quenched with 10 mL saturated NH4Cl solution and extracted with EtOAc (2×20 mL). The combined organic layers were dried and evaporated. The crude product was purified by preparative HPLC (ammonium acetate/acetonitrile) to furnish the desired compound as off-white solid (125 mg, 34%). MS (ESI): m/z=425.2 [M+H]+.
Workup
- customthe resulting reaction mixture
- stirringthe reaction mixture was stirred for another 12 hours at 25° C
- customThe reaction mixture was quenched with 10 mL saturated NH4Cl solution
- extractionextracted with EtOAc (2×20 mL)
- customThe combined organic layers were dried
- customevaporated
- customThe crude product was purified by preparative HPLC (ammonium acetate/acetonitrile)
Sources & evidence
- ORD record
- ord-44c90c3da43d4d4cad0694c48467c75c
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08987307B2
Reaction notes
Loading…