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

HRID 458303Notes

Reaction equation

HRID 458303 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
20 °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 4l of n-heptane, the reaction was evaporated to 2.91, cooled to 0° C., filtered, the residue was treated twice the same way, the third time by dissolving the residue again in 2l 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. temperaturecooled to 3–5° C.
  2. temperaturecooling
  3. temperaturethe reaction temperature was raised during 2 h to 35° C
  4. customthe reaction was evaporated to 2.91
  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 2l 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-7d53157c506a4844ad931aa2e3071844
Source dataset
uspto-grants-2007_03
Patent number
US07189756B2

Reaction notes

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