Sodium Bicarbonate → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-pyrazolylmethyl)piperazine

To a mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)piperazine (3.71 g) and 4-formyl-1-(triphenylmethyl)pyrazole (3.66 g) in 1,2-dichloroethane (80 ml) was added sodium triacetoxyborohydride (2.86 g). After stirring at room temperature for 3 hours, aqueous sodium bicarbonate solution was added to the mixture and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The resulting residue was dissolved in dichloromethane (40 ml) and added to a mixture of trifluoroacetic acid (30 ml) and anisole (15 ml). After stirring for 7.5 hours at room temperature, the mixture was quenched with 10% sodium hydroxide (150 ml) and aqueous sodium bicarbonate and extracted with dichloromethane. The extract was washed with aqueous sodium bicarbonate solution and brine successively, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (3:7) to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-pyrazolylmethyl)piperazine (2.84 g).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe extract was washed with brine
3. dry with materialdried over magnesium sulfate
4. customevaporated under reduced pressure
5. dissolutionThe resulting residue was dissolved in dichloromethane (40 ml)
6. additionadded to a mixture of trifluoroacetic acid (30 ml) and anisole (15 ml)
7. stirringAfter stirring for 7.5 hours at room temperature
8. customthe mixture was quenched with 10% sodium hydroxide (150 ml) and aqueous sodium bicarbonate
9. extractionextracted with dichloromethane
10. washThe extract was washed with aqueous sodium bicarbonate solution and brine successively
11. dry with materialdried over magnesium sulfate
12. customevaporated under reduced pressure
13. customThe residue was purified by column chromatography on silica gel using
14. additiona mixture of ethyl acetate and hexane (3:7)

ORDレコード

ord-aa7f1fa3362c4960a23029d6515c6541

出典データセット

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06924278B2