Ethyl Acetate → tert-butyl (RS)-3-(4-amino-3-chlorophenyl)pyrrolidine-1-carboxylate

HRID 571832Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]2)=[CH:4][CH:3]=1.C1C(=O)N([Cl:27])C(=O)C1.CCOC(C)=O>CN(C=O)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]2)=[CH:6][C:7]=1[Cl:27]

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of tert-butyl 3-(4-aminophenyl)pyrrolidine-1-carboxylate (2.00 g, CAS-908334-28-1) in DMF (15 ml) was added NCS (1.07 g) and the mixture was stirred at 70° C. for 1 hour. The reaction mixture was then cooled to room temperature and poured into EtOAc and extracted sequentially with water and with saturated brine. The organic layer was dried over Na2SO4 and then concentrated in vacuo. The residue was purified by column chromatography (SiO2, gradient: 0% to 55% EtOAc in hexanes) to afford tert-butyl (RS)-3-(4-amino-3-chlorophenyl)pyrrolidine-1-carboxylate (1.16 g, 51%) as a yellow oil which was used in the next step without further purification. MS (ISP): 299.0 ([{37Cl}M+H]+), 297.2 ([{35Cl}M+H]+), 243.0 ([{37Cl}M+H—C4H8]+), 241.1 ([{35Cl}M+H—C4H8]+).

Workup

temperatureThe reaction mixture was then cooled to room temperature
extractionextracted sequentially with water and with saturated brine
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography (SiO2, gradient: 0% to 55% EtOAc in hexanes)

Sources & evidence

ORD record: ord-280683f9e61f4b5cabad774882068a1d
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029370B2

Reaction notes

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