Ethanol → (2S,4S)-1-tert-butyl 2-methyl 4-bromopyrrolidine-1,2-dicarboxylate

HRID 1670609Notes

Reaction equation

HRID 1670609 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:20][O:21][C:22]([C@@H:24]1[CH2:28][C@@H:27](O)[CH2:26][N:25]1[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:23].C(Br)(Br)(Br)[Br:38].C(O)C>ClCCl>[CH3:20][O:21][C:22]([C@@H:24]1[CH2:28][C@H:27]([Br:38])[CH2:26][N:25]1[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:23]

Participants

6

Reactant 4

HCID 702EthanolHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 34176502(2S,4S)-1-tert-butyl 2-methyl 4-bromopyrrolidine-1,2-dicarboxylateYield 86.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add triphenylphosphine (0.88 mol, 231 g) in portions to a solution of (2S,4R)-4-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (0.58 mol, 144 g) and CBr4 (0.88 mol, 292 g) in dry dichloromethane (1.44 L) at 0° C. Upon complete addition, warm the reaction mixture to room temperature and stir for 4 h. Add ethanol (1.44 L) and stir for an additional 2 h. Add diethyl ether (1.44 L) to the reaction mixture, filter the precipitated triphenylphosphine oxide, and concentrate the filtrate under reduced pressure. Purify by column chromatography using 5% ethyl acetate in hexanes as eluent to obtain the title compound (155 g, 85%) as a thick oil. ES-MS m/z 308 [M+1]+.

Workup

  1. additionUpon complete addition
  2. filtrationAdd diethyl ether (1.44 L) to the reaction mixture, filter the precipitated triphenylphosphine oxide
  3. concentrationconcentrate the filtrate under reduced pressure
  4. customPurify by column chromatography

Sources & evidence

ORD record
ord-540863c3b897413384a82e9e86404e8f
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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