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

HRID 1594238Notes

Reaction equation

HRID 1594238 reaction equation
O[C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.ClCCl.C(Br)(Br)(Br)[Br:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(OCC)C.CO>[Br:22][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 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 40%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

1-(tert-Butyl) 2-methyl (2S,4R)-4-hydroxytetrahydro-1H-1,2-pyrroledicarboxylate (3) (2.0 g, 8.15 mmol) was weighed into an oven-dried flask and azeotropically dried using toluene. Dichloromethane (16 mL) and carbon tetrabromide (10.81 g, 8.15 mmol) were added and the solution was stirred, cooled to 0° C. and treated with triphenylphosphine (8.5 g, 32.41 mmol). The mixture was stirred for 5 h at 0° C., then methanol (1.8 mL) was added and stirring was continued overnight at room temperature. The mixture was diluted with diethyl ether (80 ml) and the resulting suspension was filtered and washed with diethyl ether (30 ml). The solvents were combined and evaporated under reduced pressure and the crude product was purified by silica gel column chromatography eluting with hexane/ethyl acetate (19:1 to 4:1, v/v) to give the title bromide (4) (1.0 g, 40%) as a colourless oil:

Workup

  1. customazeotropically dried
  2. stirringThe mixture was stirred for 5 h at 0° C.
  3. stirringstirring
  4. filtrationthe resulting suspension was filtered
  5. washwashed with diethyl ether (30 ml)
  6. customevaporated under reduced pressure
  7. customthe crude product was purified by silica gel column chromatography
  8. washeluting with hexane/ethyl acetate (19:1 to 4:1

Sources & evidence

ORD record
ord-0f2c5c2bafce46e7bd7a5b878f2781cd
Source dataset
uspto-grants-2007_11
Patent number
US07300929B2

Reaction notes

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