Ethyl chloroformate → 1-(4-Methoxy-benzoyl)-pyrrolidine-3,3-dicarboxylic acid diethyl ester

HRID 2060236Notes

Reaction equation

C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:11]([O:13][C:14]([CH:16]1[CH2:20][CH2:19][N:18]([C:21](=[O:30])[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[CH2:17]1)=[O:15])[CH3:12].Cl[C:32]([O:34][CH2:35][CH3:36])=[O:33]>O1CCCC1>[CH2:11]([O:13][C:14]([C:16]1([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:20][CH2:19][N:18]([C:21](=[O:30])[C:22]2[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=2)[CH2:17]1)=[O:15])[CH3:12]

Participants

Conditions

Temperature: -70 °C

Procedure

Lithium bis(trimethylsilyl)amide (1000 mL of a 1.0M solution in tetrahydrofuran, 1.0 mol) was added to a stirred solution of 1-(4-methoxy-benzoyl)-pyrrolidine-3-carboxylic acid ethyl ester (±) (268 g, 0.97 mol) (see Preparation 2) in THF (1600 mL) at −70° C. The mixture was stirred for 20 mins at −70° C. then ethyl chloroformate (104 mL, 1.09 mol) was added over 15 minutes. The resulting mixture was stirred at −60° C. for 1 hour. The reaction mixture was quenched with 10% citric acid aqueous solution (1200 mL) at −50° C. then warmed to room temperature. The organic layer was separated, washed with saturated aqueous NaHCO3 (1200 mL) and water (1200 mL) then concentrated under reduced pressure to afford the title compound as an orange oil (316.0 g, 94%).

Workup

stirringThe resulting mixture was stirred at −60° C. for 1 hour
customThe reaction mixture was quenched with 10% citric acid aqueous solution (1200 mL) at −50° C.
temperaturethen warmed to room temperature
customThe organic layer was separated
washwashed with saturated aqueous NaHCO3 (1200 mL) and water (1200 mL)
concentrationthen concentrated under reduced pressure

Sources & evidence

ORD record: ord-4522435021274fd3a1cbd5ed93c1147b
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278343B2

Reaction notes

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