Water → tert-butyl (3S,4R)-3-{[(4-chlorophenyl)carbonyl]amino}-4-(3,4-dichlorophenyl)pyrrolidine-1-carboxylate

HRID 1260943Notes

Reaction equation

HRID 1260943 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][C@H:13]1[C@H:17]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)[CH2:16][N:15]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:14]1.C(N(CC)CC)C.[Cl:40][C:41]1[CH:49]=[CH:48][C:44]([C:45](Cl)=[O:46])=[CH:43][CH:42]=1.O>C(#N)C>[Cl:40][C:41]1[CH:49]=[CH:48][C:44]([C:45]([NH:12][C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH2:16][N:15]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:14]2)=[O:46])=[CH:43][CH:42]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 85014-Chlorobenzoyl chlorideHCID 86631350tert-butyl (3S,4R)-3-amino-4-(3,4-dichlorophenyl)pyrrolidine-1-carboxylate p-toluenesulfonate

Product 1

HCID 57741764tert-butyl (3S,4R)-3-{[(4-chlorophenyl)carbonyl]amino}-4-(3,4-dichlorophenyl)pyrrolidine-1-carboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of the compound (1.1 g) obtained in step 6 and triethylamine (664 μL) in acetonitrile (10 mL) was added 4-chlorobenzoyl chloride (308 μL) at 0° C., and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate solution and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 10→40% ethyl acetate/hexane) to give the title compound (0.80 g, 78%) as a white powder.

Workup

  1. extractionthe resultant product was extracted with ethyl acetate
  2. washThe organic layer was washed with aqueous sodium hydrogen carbonate solution and brine
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 10→40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-79093136887146f48b1912106db47a23
Source dataset
uspto-grants-2013_06
Patent number
US08470816B2

Reaction notes

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