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

HRID 1006774Notes

Reaction equation

HRID 1006774 reaction equation
[Cl-].[CH3:2][O:3][C:4]([C@@H:6]1[CH2:10][C@@H:9](O)[CH2:8][N:7]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:5].C(Cl)[Cl:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CCCCCCC.C(Cl)(Cl)(Cl)Cl>[CH3:2][O:3][C:4]([C@@H:6]1[CH2:10][C@H:9]([Cl:20])[CH2:8][N:7]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:5]

Participants

7

Reactant 4

HCID 312ChlorideHCID 6344DichloromethaneHCID 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 2

HCID 5943Carbon TetrachlorideSolventHCID 8900HeptaneSolvent

Conditions

Temperature
4 °C

Procedure

Via chloride: 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 1.61 CH2Cl2 was treated with 680 g (2.6 mol) triphenylphosphine, cooled to 3-5° C. and treated in 10 min with 1.241 (12.8 mol) CCl4, after 2 h at this temperature cooling was stopped, the reaction temperature was 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 was 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-35f9dcaf4ed74752a7ed235565cc4695
Source dataset
uspto-grants-2004_09
Patent number
US06790860B2

Reaction notes

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