Water → HCID 10687030, compound

HRID 1289254Notes

Reaction equation

HRID 1289254 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:13][C:14]([NH:16][C@@H:17]([C:27](=O)[NH2:28])[CH2:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.O>ClCCl.N1C=CC=CC=1>[CH2:6]([O:13][C:14]([NH:16][C@@H:17]([C:27]#[N:28])[CH2:18][CH2:19][C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 3

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 1085434077340-94-4

Product 1

HCID 10687030HCID 10687030, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of phosphorus oxychloride (2.05 g, 13.4 mmol) in dichloromethane (5.5 ml) was added during 20 minutes to a stirred solution of tert-butyl (4R)-4-(benzyloxycarbonylamino)-4-carbamoylbutyrate (3.0 g, 8.9 mmol) in dry pyridine (16 ml) at -5° C. under argon. The mixture was allowed to warm to room temperature and after 25 hours was poured into cold water (110 ml). The products were extracted with ethyl acetate (4×40 ml) and the combined ethyl acetate solution was washed successively with 10% aqueous citric acid solution (4×15 ml) and water (25 ml), then dried (Na2SO4) and evaporated. Toluene (4×25 ml) was added and evaporated and the residue was chromatographed with increasingly polar mixtures of hexane and ethyl acetate (100:0 to 2:1) as eluant to give tert-butyl (4R)-4-(benzyloxycarbonylamino)-4-cyanobutyrate (2.433 g, 86%) as a pale yellow oil.

Workup

  1. extractionThe products were extracted with ethyl acetate (4×40 ml)
  2. washthe combined ethyl acetate solution was washed successively with 10% aqueous citric acid solution (4×15 ml) and water (25 ml)
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. additionToluene (4×25 ml) was added
  6. customevaporated
  7. customthe residue was chromatographed
  8. temperaturewith increasingly polar mixtures of hexane and ethyl acetate (100:0 to 2:1) as eluant

Sources & evidence

ORD record
ord-ad4728e798cf4720b4d4ba80ada20bf7
Source dataset
uspto-grants-1998_05
Patent number
US05747499

Reaction notes

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