Potassium Hydroxide → HCID 15788478, compound

HRID 975996Notes

Reaction equation

HRID 975996 reaction equation
[C:1]([O:5][C:6]([C@@H:8]1[CH2:12][S:11][C@H:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=2[F:20])[N:9]1[C:21](=[O:38])[CH2:22][NH:23][C:24](=[O:37])[NH:25][C:26]1[CH:27]=[C:28]([CH2:32][C:33]([O:35]C)=[O:34])[CH:29]=[CH:30][CH:31]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+]>O.CO.[OH-].[Na+]>[C:1]([O:5][C:6]([C@@H:8]1[CH2:12][S:11][C@H:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=2[F:20])[N:9]1[C:21](=[O:38])[CH2:22][NH:23][C:24](=[O:37])[NH:25][C:26]1[CH:27]=[C:28]([CH2:32][C:33]([OH:35])=[O:34])[CH:29]=[CH:30][CH:31]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 86750542HCID 86750542, compound

Product 1

HCID 15788478HCID 15788478, compoundYield 7.5%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

The operation is carried out in a fashion similar to that described in Example 77, but starting from 0.68 g of methyl (2R,4R)-3-{3-{2-[4-tert-butoxycarbonyl-2-(2,3-difluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}phenylacetate in 6 cm3 of a water/methanol (30/70 by volume) mixture and 0.08 g of potassium hydroxide. The crude product (0.45 g) is dissolved in 7.5 cm3 of 0.1N aqueous sodium hydroxide solution. The solution thus obtained is washed with 2 times 10 cm3 of diethyl ether, brought to a pH of 2 by addition of a 1N aqueous sulphuric acid solution, then extracted with 2 times 20 cm3 of ethyl acetate. The organic phases are combined, dried over magnesium sulphate and concentrated to dryness under reduced pressure at 40° C. The product obtained is purified by chromatography on silica [eluent:methylene chloride/methanol (80/20 by volume)]. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure at 40° C. 0.05 g of (2R,4R)-3-{3-{2-[4-tert-Butoxycarbonyl-2-(2,3-difluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}phenylacetic acid is thus obtained in the form of an amorphous product.

Workup

  1. customThe solution thus obtained
  2. washis washed with 2 times 10 cm3 of diethyl ether
  3. additionbrought to a pH of 2 by addition of a 1N aqueous sulphuric acid solution
  4. extractionextracted with 2 times 20 cm3 of ethyl acetate
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated to dryness under reduced pressure at 40° C
  7. customThe product obtained
  8. customis purified by chromatography on silica [eluent:methylene chloride/methanol (80/20 by volume)]
  9. additionThe fractions containing the expected product
  10. concentrationconcentrated to dryness under reduced pressure at 40° C

Sources & evidence

ORD record
ord-cbb5a17322cc451f8d476616e25e5372
Source dataset
uspto-grants-1997_03
Patent number
US05610144

Reaction notes

Loading…