1-Chloroethyl chloroformate → (3S,4R)-methyl 4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylate

HRID 2200279Notes

Reaction equation

HRID 2200279 reaction equation
ClC(OC(Cl)C)=O.C([N:15]1[CH2:19][C@@H:18]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[C@H:17]([C:28]([O:30][CH3:31])=[O:29])[CH2:16]1)C1C=CC=CC=1>ClCCCl>[Cl:27][C:22]1[CH:21]=[C:20]([C@@H:18]2[CH2:19][NH:15][CH2:16][C@H:17]2[C:28]([O:30][CH3:31])=[O:29])[CH:25]=[CH:24][C:23]=1[Cl:26]

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 66617857(3S,4R)-methyl 1-benzyl-4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylate

Product 1

HCID 51441219(3S,4R)-methyl 4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylateYield 98.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-Chloroethyl chloroformate (1.5 mL, 13.9 mmol) was added to a solution of (3S,4R)-methyl 1-benzyl-4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylate (4.20 g, 11.5 mmol) in DCE (50 mL) at 0° C. The mixture was refluxed for 1 hour. After cooling, the solvent was removed under vacuum at 65° C. for 1 hour. MeOH (50 mL) was added to the residue and refluxed for 1 hour. The MeOH was removed. The solid was redissolved in CHCl3 and treated with saturated Na2CO3. The aqueous layer was separated and extracted with CHCl3 (2×30 mL). The organic phase was combined and dried. The solvent was removed to afford (3S,4R)-methyl 4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylate (3.1 g, 98%). (LCMS (APCI+) [M+H]+ 274.1; Rt: 2.25 min.).

Workup

  1. temperatureThe mixture was refluxed for 1 hour
  2. temperatureAfter cooling
  3. customthe solvent was removed under vacuum at 65° C. for 1 hour
  4. additionMeOH (50 mL) was added to the residue
  5. temperaturerefluxed for 1 hour
  6. customThe MeOH was removed
  7. dissolutionThe solid was redissolved in CHCl3
  8. additiontreated with saturated Na2CO3
  9. customThe aqueous layer was separated
  10. extractionextracted with CHCl3 (2×30 mL)
  11. customdried
  12. customThe solvent was removed

Sources & evidence

ORD record
ord-cd554d477ff04098b1e2e30a594e68cb
Source dataset
uspto-grants-2016_06
Patent number
US09359340B2

Reaction notes

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