HCID 178503205, compound → HCID 178503204, compound

HRID 724276Notes

Reaction equation

HRID 724276 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:27][C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([S:34][CH3:35])[CH:29]=3)=[N:22][CH:23]=[C:24]([F:26])[CH:25]=2)=[O:19])[CH2:13][CH2:12]1)=[O:10])C1C=CC=CC=1>C(O)=O.CO.[Pd]>[F:26][C:24]1[CH:25]=[C:20]([C:18]([NH:17][C@@H:14]2[CH2:15][CH2:16][C@H:11]([C:9]([OH:10])=[O:8])[CH2:12][CH2:13]2)=[O:19])[C:21]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([S:34][CH3:35])[CH:29]=2)=[N:22][CH:23]=1

Participants

5

Reactant 1

HCID 178503205HCID 178503205, compound

Product 1

HCID 178503204HCID 178503204, compoundYield 48.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 284Formic AcidSolvent2×HCID 887MethanolSolvent2×

Procedure

cis-4-{[5-Fluoro-2-(3-methylsulfanyl-phenoxy)-pyridine-3-carbonyl]-amino}-cyclohexanecarboxylic acid benzyl ester (1.75 g, 3.54 mmol) was dissolved in a solution of 4.4% formic acid in methanol (40 ml) and this was added dropwise to a suspension of palladium black (2 g) in 4.4% formic acid in methanol (120 ml) at room temperature under nitrogen. The mixture was stirred for 2 h, then filtered through arbocel washing with methanol (5×50 ml). The filtrates were concentrated under reduced pressure and basified to pH10 with 1M sodium hydroxide solution (50 ml). The aqueous phase was extracted with diethylether (3×50 ml) then acidified to pH1 with concentrated hydrochloric acid. After extraction with diethylether (3×50 ml) the combined organic extracts were washed with water (10 ml), dried over MgSO4 and the solvent removed under reduced pressure to give cis-4-{[5-Fluoro-2-(3-methylsulfanyl-phenoxy)-pyridine-3-carbonyl]-amino}-cyclohexanecarboxylic acid (691 mg) as a white solid.

Workup

  1. filtrationfiltered through arbocel washing with methanol (5×50 ml)
  2. concentrationThe filtrates were concentrated under reduced pressure and basified to pH10 with 1M sodium hydroxide solution (50 ml)
  3. extractionThe aqueous phase was extracted with diethylether (3×50 ml)
  4. extractionAfter extraction with diethylether (3×50 ml) the combined organic extracts
  5. washwere washed with water (10 ml)
  6. dry with materialdried over MgSO4
  7. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-6a7bedebd1324aca9d60731febe0cc5c
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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