1,2-Dichloroethane → HCID 68752619, compound

HRID 333308Notes

Reaction equation

HRID 333308 reaction equation
[C:1]([CH:3]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=1)[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2].[NH4+].[OH-].[CH2:22]([O:29][C:30](=[O:40])[CH2:31][C:32]1([C:37](O)=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CCO.CN(C=O)C.[Ni]>[CH2:22]([O:29][C:30](=[O:40])[CH2:31][C:32]1([C:37]([NH:2][CH2:1][CH:3]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)[C:4]([O:6][C:7]([CH3:8])([CH3:10])[CH3:9])=[O:5])=[O:38])[CH2:33][CH2:34][CH2:35][CH2:36]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 14923Ammonium HydroxideHCID 181649HOAtHCID 596082261-(2-(Benzyloxy)-2-oxoethyl)cyclopentanecarboxylic acidHCID 68748010Tert-butyl 2-cyano-3-(3,4-dichlorophenyl)propanoate

Product 1

HCID 68752619HCID 68752619, compoundYield 46.3%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of tert-butyl 2-cyano-3-(3,4-dichlorophenyl)propanoate (100 mg, 0.333 mmol), Raney 2800 nickel (slurry in water) (156 mg, 2.67 mmol) and NH4OH (1.297 ml, 33.3 mmol) in EtOH (3 ml) was allowed to stir under hydrogen at room temperature for 14 hours. The reaction mixture was filtered and concentrated under reduced pressure to give a crude material (93 mg). A solution of the crude material, 1-(2-(benzyloxy)-2-oxoethyl)cyclopentanecarboxylic acid (87 mg, 0.333 mmol), EDC (83 mg, 0.433 mmol) and HOAt (58.9 mg, 0.433 mmol) in DMF (1 ml) was allowed to stir at room temperature for 2 hours. The reaction was quenched with H2O, and the product was extracted with EtOAc and washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 20:80) to give tert-butyl 3-(1-(2-(benzyloxy)-2-oxoethyl)cyclopentanecarboxamido)-2-(3,4-dichlorobenzyl)propanoate (84.5 mg); Retention time=1.70 minutes (condition B); MS (m+1)=548.2; 1H NMR (400 MHz, CDCl3, data for major rotamer) δ ppm 1.37 (s, 9H) 1.61-1.70 (m, 6H) 2.00-2.07 (m, 2H) 2.66-2.84 (m, 5H) 3.26-3.48 (m, 2H) 5.08 (s, 2H) 6.43-6.46 (app t, 1H) 7.02-7.05 (m, 1H) 7.29-7.36 (m, 7H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated under reduced pressure
  3. customto give a crude material (93 mg)
  4. stirringto stir at room temperature for 2 hours
  5. customThe reaction was quenched with H2O
  6. extractionthe product was extracted with EtOAc
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe obtained residue was purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 20:80)

Sources & evidence

ORD record
ord-469f8a5b55e04dbcbed0e63af02837ee
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

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