1,2-Dichloroethane → HCID 69939642, compound

HRID 1058313Notes

Reaction equation

HRID 1058313 reaction equation
C(Cl)CCl.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:14][N:15]2[CH2:18][CH:17]([OH:19])[CH2:16]2)=[C:10]([CH:13]=1)[CH2:11][NH2:12].[C:20]([N:27]1[CH2:34][CH2:33][CH2:32][C@H:28]1[C:29](O)=[O:30])([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C1C=NC2N(O)N=NC=2C=1>CN(C=O)C>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:14][N:15]2[CH2:16][CH:17]([OH:19])[CH2:18]2)=[C:10]([CH:13]=1)[CH2:11][NH:12][C:29](=[O:30])[C@@H:28]1[CH2:32][CH2:33][CH2:34][N:27]1[C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 181649HOAtHCID 18672299HCID 18672299, compound

Product 1

HCID 69939642HCID 69939642, compoundYield 9.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (1.51 g, 7.87 mmol) was added to a stirred mixture of 5-chloro-2-[(3-hydroxyazetidin-1-yl)methyl]benzylamine (1.19 g, 5.25 mmol), N-Boc-L-proline (1.13 g, 5.25 mmol) and HOAT (0.36 g, 2.62 mmol) in DMF (9 mL). After 16 h the mixture was concentrated and the residue was partitioned between EtOAc and 10% NaHCO3. The organic layer was washed with water and brine, dried (Na2SO4)and evaporated. The residue was partitioned between EtOAc and 1M citric acid. The aqueous layer was made neutral with NaHCO3 and was extracted into CH2Cl2. The organic layer was evaporated and the residue was purified by chromatography on silica (ammonia saturated CHCl3/MeOH, 95:5) to give N-{5-chloro-2-[(3-hydroxyazetidin-1-yl)methyl]benzyl}-1-(tert-butoxycarbonyl)-L-prolinamide (210 mg) as a glass: MS: 424.5 (M+1).

Workup

  1. concentrationAfter 16 h the mixture was concentrated
  2. customthe residue was partitioned between EtOAc and 10% NaHCO3
  3. washThe organic layer was washed with water and brine, dried (Na2SO4)and
  4. customevaporated
  5. customThe residue was partitioned between EtOAc and 1M citric acid
  6. extractionwas extracted into CH2Cl2
  7. customThe organic layer was evaporated
  8. customthe residue was purified by chromatography on silica (ammonia saturated CHCl3/MeOH, 95:5)

Sources & evidence

ORD record
ord-a6834300403446d6913336c75309e170
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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