반응 #1885053

반응 방정식

(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

수율 65.1%

용매

MeOH

MeOH

반응 조건

후처리

1. 1
   농축The reaction mixture was concentrated under reduced pressure
2. 2
   기타to provide 9.5 g of a brown waxy solid
3. 3
   workup.WAITto stand at RT overnight
4. 4
   기타The solid was collected
5. 5
   세척washed with diethyl ether (2×25 mL)
6. 6
   기타dried under vacuum

실험 절차

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.

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