反应详情

To a solution of 2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-benzaldehyde (200.0 mg, 0.391 mmoles) in ethanol (3.0 mL) was added N-methyl benzylamine (61 μL, 0.469 mmol) and benzotriazole (56 mg, 0.469 mmoles) and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated to remove ethanol and the residue was taken up in toluene (6.0 mL), cooled to 0° C. and ethyl magnesium chloride (0.78 mL, 1.564 mmoles of a 2M solution in ether) was added. The reaction was allowed to warm to room temperature and stirred for 2 hours. The reaction mixture was quenched with saturated aqueous NH4Cl. Ether was added and the mixture was stirred for 5 minutes, To the mixture was added 1N NaOH to achieve pH of 10. The aqueous layer was extracted with ether and the combined organic layer was dried over sodium sulfate and concentrated to give a yellow oil. The crude product was purified using silica gel chromatography on the ISCO Combiflash system (Teledyne ISCO, Lincoln, Nebr., USA) with a gradient of 1-3% methanol in dichloromethane to yield the title compound (242.7 mg, 96% yield) as light yellow oil. MS (ES+) Calc: 608.5, Found: 609.1 (M+1).

1. concentrationThe reaction mixture was concentrated
2. customto remove ethanol
3. temperaturecooled to 0° C.
4. additionethyl magnesium chloride (0.78 mL, 1.564 mmoles of a 2M solution in ether) was added
5. temperatureto warm to room temperature
6. stirringstirred for 2 hours
7. customThe reaction mixture was quenched with saturated aqueous NH4Cl
8. additionEther was added
9. stirringthe mixture was stirred for 5 minutes, To the mixture
10. additionwas added 1N NaOH
11. extractionThe aqueous layer was extracted with ether
12. dry with materialthe combined organic layer was dried over sodium sulfate
13. concentrationconcentrated
14. customto give a yellow oil
15. customThe crude product was purified