反应详情

Lithium aluminum hydride (208 g, 5.0 eq) is suspended in 3.9 L of methyl tert-butyl ether and the suspension is stirred for 10 min. A solution of 1-(1-trifluoromethyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid ethyl ester (260 g, 0.93 mol) in 1.3 L of methyl tert-butyl ether is added dropwise at <30° C. The mixture is refluxed for 20 h and cooled to 0˜10° C. 500 mL of water are added at 0˜10° C. and the mixture is stirred for 30 min. The suspension is filtered and the cake is washed with 1.8 L of methyl tert-butyl ether. The filtrate is concentrated to ˜3 L of volume at <35° C. under vacuum. The solvent is displaced with tetrahydrofuran (1.0 L×2) and concentrated to provide 212 g of the title compound in 96.8% purity.

1. temperatureThe mixture is refluxed for 20 h
2. temperaturecooled to 0˜10° C
3. stirringthe mixture is stirred for 30 min
4. filtrationThe suspension is filtered
5. washthe cake is washed with 1.8 L of methyl tert-butyl ether
6. concentrationThe filtrate is concentrated to ˜3 L of volume at <35° C. under vacuum
7. concentrationconcentrated