Methanol → HCID 54052487, compound

HRID 976010Notes

Reaction equation

HRID 976010 reaction equation
CO.[C:3]([O:7][C:8]([C@@H:10]1[CH2:14][S:13][C@H:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=2[F:22])[N:11]1[C:23](=[O:47])[CH2:24][NH:25][C:26](=[O:46])[NH:27][C:28]1[CH:29]=[C:30]([CH:34]([CH3:45])[C:35]([O:37]CC2C=CC=CC=2)=[O:36])[CH:31]=[CH:32][CH:33]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].C([O-])=O.[NH4+]>[Pd].[OH-].[Na+]>[C:3]([O:7][C:8]([C@@H:10]1[CH2:14][S:13][C@H:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=2[F:22])[N:11]1[C:23](=[O:47])[CH2:24][NH:25][C:26](=[O:46])[NH:27][C:28]1[CH:29]=[C:30]([CH:34]([CH3:45])[C:35]([OH:37])=[O:36])[CH:31]=[CH:32][CH:33]=1)=[O:9])([CH3:5])([CH3:4])[CH3:6]

Participants

6

Reactant 3

HCID 887MethanolHCID 2723923Ammonium formateHCID 67713070HCID 67713070, compound

Product 1

HCID 54052487HCID 54052487, compoundYield 84.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
25 °C

Procedure

In an inert atmosphere 20 cm3 of methanol are slowly added to a flask containing 1.38 g of benzyl 2-{3-{3-{2-[(2R,4R)-4-tert-butoxycarbonyl-2-(2,3-difluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}phenyl}propionate (B form), 0.85 g of ammonium formate and 1.38 g of 10% palladium on charcoal. The reaction mixture is heated under reflux for 1 hour, then cooled to a temperature in the vicinity of 25° C. The catalyst is then removed by filtration and the filtrate is concentrated to dryness under reduced pressure at 40° C. The residue obtained is dissolved in 20 cm3 of a 0.1N aqueous sodium hydroxide solution and washed with two times 10 cm3 of diethyl ether. The aqueous phase is brought to a pH of 2 by addition of a 1N aqueous sulphuric acid solution. The precipitated product is separated by filtration, washed with 2 times 10 cm3 of water and dried in air. 1.0 g of 2-{3-{3-{2-[(2R,4R)-4-tert-butoxycarbonyl-2-(2,3-difluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}phenyl}propionic acid (B form), melting at 130° C., is thus obtained. [α]D20 =+82°±2° (C=0.707%; DMF)

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureunder reflux for 1 hour
  3. customThe catalyst is then removed by filtration
  4. concentrationthe filtrate is concentrated to dryness under reduced pressure at 40° C
  5. customThe residue obtained
  6. washwashed with two times 10 cm3 of diethyl ether
  7. additionThe aqueous phase is brought to a pH of 2 by addition of a 1N aqueous sulphuric acid solution
  8. customThe precipitated product is separated by filtration
  9. washwashed with 2 times 10 cm3 of water
  10. customdried in air

Sources & evidence

ORD record
ord-a6a5955d37164c9aac13a8579e02a965
Source dataset
uspto-grants-1997_03
Patent number
US05610144

Reaction notes

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