1-Chloro-4-(chloromethyl)benzene → (R)-tert-Butyl (1-(4-chlorobenzyl)pyrrolidin-3-yl)carbamate

HRID 2187761Notes

Reaction equation

[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Cl)=[CH:4][CH:3]=1.[C:10]([O:14][C:15]([NH:17][CH:18]1[CH2:22][CH2:21][NH:20][CH2:19]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]>CN(C=O)C>[C:10]([O:14][C:15]([NH:17][CH:18]1[CH2:22][CH2:21][N:20]([CH2:6][C:5]2[CH:8]=[CH:9][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH2:19]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

Conditions

Temperature: 70 °C

Procedure

4-Chlorobenzyl chloride (4.15 g, 25.8 mmol) and 2Pr2NEt (6.67 g, 51.6 mmol) were added to a solution of 3-{(tert-butoxycarbonyl)amino}pyrrolidine (4.81 g, 25.8 mmol) in DMF (50 mL). The reaction mixture was stirred at 70° C. for 15 h and the solvent was removed under reduced pressure. Recrystallization (CH3CN, 50 mL) provided the desired material, 3-(tert-butoxycarbonyl)amino-1-(4-chlorobenzyl)pyrrolidine as a pale yellow solid (6.43 g, 80.2%): 1H NMR (CDCl3, 300 MHz) δ 1.37 (s, 9 H), 1.5-1.7 (br, 1 H), 2.1-2.4 (m, 2 H), 2.5-2.7 (m, 2 H), 2.83 (br, 1 H), 3.57 (s, 2 H), 4.1-4.3 (br, 1 H), 4.9-5.1 (br, 1 H), 7.15-7.35 (br, 4 H); The purity was determined by RPLC/MS (98%); ESI/MS m/e 311.0 (M++H, C16H24ClN2O2).

Workup

customthe solvent was removed under reduced pressure
customRecrystallization (CH3CN, 50 mL)

Sources & evidence

ORD record: ord-d147f7f4af3e4b76aeb0e2a69a333892
Source dataset: uspto-grants-2002_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06410566B1

Reaction notes

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