反应详情

To a stirred solution of 0.44 g of α-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester (prepared above as Aldehyde 5) and 0.55 g of 4-(4-benzyl-5-methyl-1H-pyrazole-3(2H)-on-2-yl)-piperidine in 3 mL 1,2-dichloroethane, 0.5 mL MeOH and 0.1 mL HOAc is added 0.3 g of powdered molecular sieves (4A). After 15 minutes, 0.1 g of sodium triacetoxyborohydride was added and stirring was continued overnight. The reaction mixture was poured into a rapidly stirred mixture of ethyl acetate and saturated sodium bicarbonate solution (˜15 mL each). After 15 minutes the mixture was filtered through Celite, the aqueous layer separated and extracted with 25 mL ethyl acetate. The combined organic layers were washed with saturated sodium bicarbonate solution, water, then brine, dried with sodium sulfate and concentrated under reduced pressure to give 0.068 g of α-(R)-(3-(S)-((4-(4-benzyl-5-methyl-1H-pyrazol-3(2H)-on-2-yl)-piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester suitable for use in the next step. ESI-MS 691.3 (M+H); HPLC A: 3.20 min.

1. waitwas continued overnight
2. filtrationAfter 15 minutes the mixture was filtered through Celite
3. customthe aqueous layer separated
4. extractionextracted with 25 mL ethyl acetate
5. washThe combined organic layers were washed with saturated sodium bicarbonate solution, water
6. dry with materialbrine, dried with sodium sulfate
7. concentrationconcentrated under reduced pressure