HCID 178503264, compound → HCID 178503263, compound

HRID 724281Notes

Reaction equation

HRID 724281 reaction equation
C([O:8][C:9]([C@H:11]1[CH2:16][CH2:15][C@@H:14]([NH:17][C:18]([C:20]2[C:21]([O:26][C:27]3[CH:32]=[CH:31][C:30]([S:33][CH3:34])=[CH:29][CH:28]=3)=[N:22][CH:23]=[CH:24][CH:25]=2)=[O:19])[CH2:13][CH2:12]1)=[O:10])C1C=CC=CC=1>C(O)=O.CO.CN(C)C=O.[Pd]>[CH3:34][S:33][C:30]1[CH:29]=[CH:28][C:27]([O:26][C:21]2[C:20]([C:18]([NH:17][C@@H:14]3[CH2:13][CH2:12][C@H:11]([C:9]([OH:10])=[O:8])[CH2:16][CH2:15]3)=[O:19])=[CH:25][CH:24]=[CH:23][N:22]=2)=[CH:32][CH:31]=1

Participants

6

Reactant 1

HCID 178503264HCID 178503264, compound

Product 1

HCID 178503263HCID 178503263, compoundYield 76.5%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 284Formic AcidSolvent2×HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolvent

Procedure

cis-4-{[2-(4-methylsulfanyl-phenoxy)-pyridine-3-carbonyl]-amino}-cyclohexanecarboxylic acid benzyl ester (4.35 g, 9.13 mmol) was dissolved in a solution of 4.4% formic acid in methanol (100 ml) and dimethylformamide (25 ml) and this was added to a suspension of palladium black (5 g) in 4.4% formic acid in methanol (300 ml) at room temperature under nitrogen. The mixture was stirred for 2.5 h, then filtered through arbocel washing with methanol (4×200 ml). The filtrates were concentrated under reduced pressure and the residue was azeotroped with toluene (2×50 ml). The residue was then diluted with water (50 ml) and basified to pH10 with 1M sodium hydroxide pellets. The aqueous phase was extracted with diethylether (2×50 ml) then acidified to pH1 with concentrated hydrochloric acid. After extraction with diethylether (5×50 ml) the combined organic extracts were washed with water (20 ml), dried over MgSO4 and the solvent removed under reduced pressure to give cis-4-{[2-(4-methylsulfanyl-phenoxy)-pyridine-3-carbonyl]-amino}-cyclohexanecarboxylic acid (2.7 g) as a white solid.

Workup

  1. filtrationfiltered through arbocel washing with methanol (4×200 ml)
  2. concentrationThe filtrates were concentrated under reduced pressure
  3. customthe residue was azeotroped with toluene (2×50 ml)
  4. additionThe residue was then diluted with water (50 ml)
  5. extractionThe aqueous phase was extracted with diethylether (2×50 ml)
  6. extractionAfter extraction with diethylether (5×50 ml) the combined organic extracts
  7. washwere washed with water (20 ml)
  8. dry with materialdried over MgSO4
  9. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-7abcf9ba409149af968e82994cd5d8cc
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

Loading…