Water → HCID 69844883, compound

HRID 393469Notes

Reaction equation

HRID 393469 reaction equation
[CH3:1][O:2][C:3](=[O:35])[C@H:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]2[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=2[Cl:34])=[O:26])=[CH:20][CH:19]=1)[NH:5][C:6]([C:8]1([CH2:13][CH2:14][CH:15]=[CH2:16])[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7].[BH4-].[Na+].O.C(OCC)(=[O:41])C>C1COCC1.[Cu]Cl>[CH3:1][O:2][C:3](=[O:35])[C@H:4]([CH2:17][C:18]1[CH:19]=[CH:20][C:21]([NH:24][C:25]([C:27]2[C:28]([Cl:34])=[CH:29][CH:30]=[CH:31][C:32]=2[Cl:33])=[O:26])=[CH:22][CH:23]=1)[NH:5][C:6]([C:8]1([CH2:13][CH2:14][CH2:15][CH2:16][OH:41])[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7]

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 4311764Sodium borohydrideHCID 545023014-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[1-(3-butenyl)cyclopentyl]carbonyl]-L-phenylalanine methyl ester

Product 1

HCID 69844883HCID 69844883, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-[[(2,6-dichlorophenyl)carbonyl]arnino]-N-[[1-(3-butenyl)cyclopentyl]-carbonyl]-L-phenylalanine methyl ester (3.13 mmol, 1.62 g) and anhydrous copper (I) chloride (5.0 mmol, 500 mg) in THF (30 mL) was added solid sodium borohydride (5.0 mmol, 200 mg) at −5° C. over 5 min. After the addition, the reaction mixture was allowed to warm to room temperature and the brown reaction mixture was stirred for 36 h at which time TLC analysis of the mixture indicated the absence of starting material. Then, the excess hydride was quenched by the addition of water (5 mL) and the reaction mixture was cooled to 0° C. To this, a solution of sodium acetate (20 mL, 3.0N) was added dropwise maintaining the temperature below 10° C. this was followed by H2O2 (25 mL, 30%). After addition of hydrogen peroxide, the reaction mixture was allowed to warm to room temperature and was stirred for 3 h and followed by 1 h at 40-45° C. to complete the hydrolysis. Then, it was poured into a mixture of water (50 mL) and ethyl acetate (50 mL). The two layers were separated and the aqueous layer was extracted with ethyl acetate (2×30 mL). The comined extracts were washed with brine solution and dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent gave a crude product which was purified by silica gel column chromatography to afford 1.04 g (62%) of a white amorphous solid. HR MS (C27H32Cl2N2O5): Obs. mass, 535.1758. Calcd. mass, 535.1766, M+H).

Workup

  1. additionAfter the addition
  2. customThen, the excess hydride was quenched by the addition of water (5 mL)
  3. temperaturethe reaction mixture was cooled to 0° C
  4. additionTo this, a solution of sodium acetate (20 mL, 3.0N) was added dropwise
  5. temperaturemaintaining the temperature below 10° C.
  6. additionAfter addition of hydrogen peroxide
  7. temperatureto warm to room temperature
  8. stirringwas stirred for 3 h
  9. waitfollowed by 1 h at 40-45° C.
  10. customthe hydrolysis
  11. customThe two layers were separated
  12. extractionthe aqueous layer was extracted with ethyl acetate (2×30 mL)
  13. washThe comined extracts were washed with brine solution
  14. dry with materialdried over anhydrous magnesium sulfate
  15. filtrationFiltration of the drying agent and removal of the solvent
  16. customgave a crude product which
  17. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9101ab55861747598cf895126db51200
Source dataset
uspto-grants-2004_10
Patent number
US06806365B2

Reaction notes

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