Method for preparing Prasugrel intermediate alpha-cyclopropylcarbonyl-2-fluorobenzyl bromide
A technology of cyclopropylcarbonyl and fluorobenzyl, applied in the field of preparation of prasugrel intermediate α-cyclopropylcarbonyl-2-fluorobenzyl bromide, which can solve the problems of low selectivity, high cost, and low product purity problem, to achieve the effect of good selectivity, low cost and environmental friendliness
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Embodiment 1
[0018] Dissolve 20g (0.112mol) of cyclopropyl-2-fluorobenzyl ketone in 100mlTHF, slowly add 40g (0.1064mol ), gradually solids were precipitated, and the dropwise addition was completed in about 10 hours. After the dropwise addition, the reaction was continued at 5°C-10°C for 2 hours. After the reaction was stopped, 100ml of water was added to the reaction solution, and most of it was recovered by distillation under reduced pressure at 30°C. THF, the residual solution was extracted with 100ml and 50ml ethyl acetate, the organic layers were combined, washed with 3×50ml saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure at 40°C to obtain α-cyclopropylcarbonyl-2- The crude product of fluorobenzyl bromide was 28.3g, the yield was 97.9%, HPLC: >94%.
[0019] 1 H NMR (CDCl 3 )δppm: 0.93-1.04 (2H, m), 1.11-1.19 (2H, m), 2.11-2.17 (2H, m), 5.96 (1H, s), 7.05-7.49 (2H, m).
[0020] Mass spectrum (Cl, m / z): 259 (M + +1).
Embodiment 2
[0022] Substitute tetrahydrofuran with anhydrous diethyl ether, and other reaction steps are the same as in Example 1. After the reaction is completed, 100 ml of water is added to the reaction solution. After the layers are separated, the aqueous layer is extracted with 50 ml of diethyl ether, the organic layers are combined, and washed with 3×50 ml of saturated brine. Dry over anhydrous sodium sulfate, and remove the solvent under reduced pressure at 40°C to obtain 27.8 g of crude α-cyclopropylcarbonyl-2-fluorobenzyl bromide, with a yield of 96.2%, HPLC: >94.5%.
Embodiment 3
[0024] Dissolve 20g (0.112mol) of cyclopropyl-2-fluorobenzyl ketone in 300ml of dichloromethane, and distribute 40g (0.1064mol) of phenyltrimethylammonium tribromide (PTT) in small batches at about 10°C under stirring, First, the added reddish-brown solid dissolved, and then gradually white solid precipitated out. The addition was completed in about 8 hours, and the reaction was continued at about 10°C for 2 hours. After the reaction stopped, 100ml of water was added to the reaction solution. Extracted with dichloromethane, combined the organic layers, washed with 3×50ml saturated brine, dried over anhydrous sodium sulfate, and removed the solvent under reduced pressure at 40°C to obtain 28g of crude product of α-cyclopropylcarbonyl-2-fluorobenzyl bromide. Yield 96.9%, HPLC: >93.5%.
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