1,2-Dichloroethane → 1-[(2R)-2-cyclohexyl-2-hydroxyethanoyl]-L-prolinamide

HRID 1058231Notes

Reaction equation

HRID 1058231 reaction equation
C(Cl)CCl.ClC1C=CC(C(NC2C=CC(OC)=CC=2)C(F)(F)F)=C(C=1)C[NH:12][C:13](=[O:19])[C@@H:14]1[CH2:18][CH2:17][CH2:16][NH:15]1.[C:35]([OH:45])(=O)[C@@H:36]([CH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1)[OH:37].C1C=NC2N(O)N=NC=2C=1>CN(C=O)C>[CH:38]1([C@@H:36]([OH:37])[C:35]([N:15]2[CH2:16][CH2:17][CH2:18][C@H:14]2[C:13]([NH2:12])=[O:19])=[O:45])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 819914(2R)-2-cyclohexyl-2-hydroxyacetic acidHCID 23560081N-(5-chloro-2-{1-[(4-methoxyphenyl)amino]-2,2,2-trifluoroethyl}benzyl)-L-prolinamide

Product 1

HCID 229584211-[(2R)-2-cyclohexyl-2-hydroxyethanoyl]-L-prolinamideYield 116.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (44.0 mg, 0.23 mmol) was added to a stirred mixture of N-(5-chloro -2-{1-[(4-methoxyphenyl)amino]-2,2,2-trifluoroethyl}benzyl)-L-prolinamide (68 mg, 0.15 mmol), (R)-(−)-hexahydromandelic acid (24.2 mg, 0.15 mmol) and HOAT (10.4 mg, 0.076 mmol), in DMF (2 mL). After 16 h, the mixture was concentrated and the residue was partitioned between EtOAc and 10% NaHCO3 solution. The organic layer was washed with water and brine, dried (Na2SO4) and evaporated. The residue was purified by chromatography on silica (eluting with EtOAc/CHCl3, 1:2) to give N-(5-chloro-2-{1-[(4-methoxyphenyl)amino]-2,2,2-trifluoroethyl)}benzyl)-1-[(2R)-2-cyclohexyl-2-hydroxyethanoyl]-L-prolinamide (44.4 mg) as a glass: MS: 582.4 (M+1).

Workup

  1. concentrationthe mixture was concentrated
  2. customthe residue was partitioned between EtOAc and 10% NaHCO3 solution
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe residue was purified by chromatography on silica (eluting with EtOAc/CHCl3, 1:2)

Sources & evidence

ORD record
ord-13eff51657e14c32b35867377fce0025
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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