Carbon Tetrachloride → (2S,4S)-1-tert-butyl 2-methyl 4-chloropyrrolidine-1,2-dicarboxylate

HRID 1278990Notes

Reaction equation

HRID 1278990 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8](O)[CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)[Cl:38].CCCCCCC>C(Cl)Cl>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@H:8]([Cl:38])[CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Participants

6

Reactant 4

HCID 5943Carbon TetrachlorideHCID 8900HeptaneHCID 11776TriphenylphosphineHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 11242503(2S,4S)-1-tert-butyl 2-methyl 4-chloropyrrolidine-1,2-dicarboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
4 °C

Procedure

A solution of 374 g (1.48 mol) (2S,4R)-4-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester in 1.6 l CH2Cl2 was treated with 680 g (2.6 mol) triphenylphosphine, cooled to 3-5° C. and treated in 10 min with 1.24 l (12.8 mol) CCl4, after 2 h at this temperature cooling was stopped, the reaction temperature raised during 2 h to 35° C. It was cooled down to 20° C. and stirred for further 45 min. After addition of 4 l of n-heptane, the reaction was evaporated to 2.9 l , cooled to 0° C., filtered, the residue was treated twice the same way, the third time by dissolving the residue again in 2 l of CH2Cl2. The solvents were evaporated and filtered through silica gel with hexane/tert.-butyl-methylether 9:1 as eluent. Evaporation of the solvents gave 347 g (89%) of (2S,4S)-4-Chloro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester, MS: 246 (MH+).

Workup

  1. temperaturecooling
  2. temperaturethe reaction temperature raised during 2 h to 35° C
  3. temperatureIt was cooled down to 20° C.
  4. customthe reaction was evaporated to 2.9 l
  5. temperaturecooled to 0° C.
  6. filtrationfiltered
  7. additionthe residue was treated twice the same way
  8. dissolutionthe third time by dissolving the residue again in 2 l of CH2Cl2
  9. customThe solvents were evaporated
  10. filtrationfiltered through silica gel with hexane/tert.-butyl-methylether 9:1 as eluent
  11. customEvaporation of the solvents

Sources & evidence

ORD record
ord-4ff40945b0f64c16a209dd6107c1fed8
Source dataset
uspto-grants-2002_09
Patent number
US06444829B1

Reaction notes

Loading…