Water → Tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate

HRID 1290847Notes

Reaction equation

[Cl:1][CH2:2][C:3](Cl)=[O:4].[C:6]([O:10][C:11]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].C(N(CC)CC)C.O>C(Cl)Cl>[Cl:1][CH2:2][C:3]([N:16]1[CH2:15][CH2:14][N:13]([C:11]([O:10][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:12])[CH2:18][CH2:17]1)=[O:4]

Participants

Conditions

Temperature: 5 °C

Procedure

To an ice-cold solution of chloroacetyl chloride (1.27 g, 10 mmol) in 15 mL of methylene chloride was added N-tert-butoxycarbonylpiperazine (1.27 g, 11 mmol) in 10 mL of methylene chloride containing triethylamine (2.17 g, 20 mmol). The reaction mixture was stirred at 5° C. for 30 minutes, then warmed to room temperature and stirred for 24 hours. Water (20 mL) was added at 5° C., and the reaction mixture was diluted with methylene chloride (200 mL). The organic layer was separated, washed with saturated aqueous NaHCO3 (2×100 mL), brine (2×100 mL), dried over MgSO4, filtered, and concentrated at reduced pressure. The concentrated residue was purified by flash column chromatography on silica gel eluting with ethyl acetate to give 2.20 g (84.0%) of 1-(2-chloroacetyl)-4-(tert-butoxycarbonyl)piperazine as a yellow liquid. 1H NMR (300 MHz / CDCl3): δ 1.46 (s, 9H), 3.41-3.60 (m, 8H), 4.07 (s, 2H). HRMS: calcd for C11H19NO3 Cl1 262.1084, found 262.1079.

Workup

temperaturewarmed to room temperature
stirringstirred for 24 hours
customThe organic layer was separated
washwashed with saturated aqueous NaHCO3 (2×100 mL), brine (2×100 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated at reduced pressure
customThe concentrated residue was purified by flash column chromatography on silica gel eluting with ethyl acetate

Sources & evidence

ORD record: ord-9736a42d070e4e96888ea69466c91dd9
Source dataset: uspto-grants-1998_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05753660

Reaction notes

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