1,2-Dichloroethane → 1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-L-prolinamide

HRID 1014149Notes

Reaction equation

HRID 1014149 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:21]=[O:22])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:23]1[CH2:30][CH2:29][CH2:28][C@H:24]1[C:25]([NH2:27])=[O:26].CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:21]=[O:22])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:8]([N:23]2[CH2:30][CH2:29][CH2:28][C@H:24]2[C:25]([NH2:27])=[O:26])=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 111306L-ProlinamideHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acid

Product 1

HCID 578781271-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-L-prolinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (WO 2003101442, 38.2 g, 0.125 mol), L-prolinamide (14.3 g, 0.125 mol,) N-methyl morpholine (34.4 mL, 0.313 mol,) and HOBt (18.65 g, 0.138 mol) were dissolved in DMF (400 mL) with stirring. EDC (26.46 g, 0.138 mol) was added portionwise and the solution was stirred at room temperature for 3 hours. The majority of the DMF was removed in vacuo and the residue was diluted with ethyl acetate (1 L.) This solution was washed with cold 0.5M HCl solution (200 mL), twice with water (200 mL), saturated aqueous NaHCO3 solution, brine, and then dried over MgSO4. After filtering and evaporating, the crude material was dissolved in hot ethyl acetate (˜150 mL) with stirring. While keeping the solution hot, hexanes (˜150 mL) was added until the solution was cloudy. Cooling slowly to room temperature while stirring gave a thick slurry. The solid was filtered off and washed with 1:1 ethyl acetate:hexanes, followed by a wash with hexanes. After drying, the product 1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-L-prolinamide was obtained as a white solid (34.4 g, 69% yield). LC/MS m/z 402 (MH+)

Workup

  1. stirringthe solution was stirred at room temperature for 3 hours
  2. customThe majority of the DMF was removed in vacuo
  3. additionthe residue was diluted with ethyl acetate (1 L.) This solution
  4. washwas washed with cold 0.5M HCl solution (200 mL), twice with water (200 mL), saturated aqueous NaHCO3 solution, brine
  5. dry with materialdried over MgSO4
  6. filtrationAfter filtering
  7. customevaporating
  8. dissolutionthe crude material was dissolved in hot ethyl acetate (˜150 mL)
  9. stirringwith stirring
  10. additionhexanes (˜150 mL) was added until the solution
  11. stirringwhile stirring
  12. customgave a thick slurry
  13. filtrationThe solid was filtered off
  14. washwashed with 1:1 ethyl acetate
  15. washa wash with hexanes
  16. customAfter drying

Sources & evidence

ORD record
ord-a7c2f83595c84be0affab70bab64e92c
Source dataset
uspto-grants-2011_07
Patent number
US07982053B2

Reaction notes

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