1,1-Dimethylethyl (2S)-2-[(methoxymethylamino)carbonyl]-1-pyrrolidinecarboxylate → (S)-2-(4-chloro-benzoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

At 0° C. 4-chlorophenylmagnesiumbromide 0.9 molar in THF/toluene (66.7 ml, 60 mmol) was added over 15 minutes to a solution of (S)-2-(Methoxy-methyl-carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester CAS 115186-37-3 (5.16 g, 20 mmol) in dry THF (50 ml). The reaction mixture was warmed to ambient temperature and stirred for another 4 hours. The reaction mixture was poured on 1N HCl/ice (150 ml) and then extracted with ethyl acetate (2×100 ml). The organic layers are washed with water (2×50 ml), saturated NaCl (50 ml) and then dried over Na2SO4. After evaporation of the solvent, the crude product (7.5 g in the form of a yellow oil) was purified by flash chromatography over silica gel 150 g, (eluent:cyclohexane/ethyl acetate 9:1) to afford 4.3 g (69.4% of theory) of (S)-2-(4-chloro-benzoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a as a white solid m.p. 117-122° C.

1. customAt 0° C
2. extractionextracted with ethyl acetate (2×100 ml)
3. washThe organic layers are washed with water (2×50 ml), saturated NaCl (50 ml)
4. dry with materialdried over Na2SO4
5. customAfter evaporation of the solvent
6. customthe crude product (7.5 g in the form of a yellow oil) was purified by flash chromatography over silica gel 150 g, (eluent:cyclohexane/ethyl acetate 9:1)

ORD record

ord-e69cd3ca11624c20a4aea094c241d6ab

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08623902B2