تفاعل #1885053

معادلة التفاعل

(R)-5-(2-(3,5-difluorophenylamino)ethyl)-2,2-dimethyl-1,3-dioxolan-4-one

p-toluensulfonic acid monohydrate

diethyl ether

→

(R)-1-(3,5-difluorophenyl)-3-hydroxypyrrolidin-2-one

المردود 65.1%

المذيبات

MeOH

MeOH

ظروف التفاعل

المعالجة

1. 1
   تركيزThe reaction mixture was concentrated under reduced pressure
2. 2
   أخرىto provide 9.5 g of a brown waxy solid
3. 3
   workup.WAITto stand at RT overnight
4. 4
   أخرىThe solid was collected
5. 5
   غسيلwashed with diethyl ether (2×25 mL)
6. 6
   أخرىdried under vacuum

الإجراء التجريبي

A stirred solution of (R)-5-(2-(3,5-difluorophenylamino)ethyl)-2,2-dimethyl-1,3-dioxolan-4-one (8.0 g, 29.5 mmol) and p-toluensulfonic acid monohydrate (508 mg, 2.95 mmol) in MeOH (75 mL) under nitrogen was heated to 70° C. for 75 minutes. The reaction mixture was slowly cooled to RT and then continued to stir at RT overnight. The reaction mixture was concentrated under reduced pressure to provide 9.5 g of a brown waxy solid. The solid was dissolved in MeOH (10 mL) and diethyl ether (100 mL) was added. The solution was allowed to stand at RT overnight. The solid was collected, washed with diethyl ether (2×25 mL) and dried under vacuum to provide (R)-1-(3,5-difluorophenyl)-3-hydroxypyrrolidin-2-one as a tan solid (4.09 g, 19.2 mmol, 65%). 1H-NMR (400 MHz, CDCl3) δ 7.35-7.27 (m, 2H), 6.68-6.63 (m, 1H), 4.51 (dd, J=8.3, 9.8 Hz, 1H), 3.85-3.71 (m, 2H), 3.08 (s, 1H), 2.69-2.62 (m, 1H) and 2.19-2.07 (m, 1H) ppm. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=214.1; tR=0.97 min.

المصدر