Water → HCID 10408884, compound

HRID 73173Notes

Reaction equation

HRID 73173 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=2)=[CH:8][C:9]=1[N:10]([CH:20]([CH3:22])[CH3:21])[C:11]([CH:13]1[CH2:18][CH2:17][CH:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].O.[Li+].[OH-]>O1CCOCC1>[F:29][C:25]1[CH:24]=[C:23]([C:7]2[S:6][C:5]([C:3]([OH:4])=[O:2])=[C:9]([N:10]([CH:20]([CH3:22])[CH3:21])[C:11]([CH:13]3[CH2:18][CH2:17][CH:16]([CH3:19])[CH2:15][CH2:14]3)=[O:12])[CH:8]=2)[CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 597523165-(3-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 10408884HCID 10408884, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

5-(3-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (25 mg, 0.060 mmol) was dissolved in a 4:1 mixture of dioxane:H2O (0.8 mL) and then LiOH 1N (0.3 ml, 0.300 mmol) was added. After 3 hours of stirring at room temperature, solvents were removed and then partitioned between 10 ml of H2O acidified to pH 4 and 10 ml of EtOAc. The organic layer was separated and the aqueous phase was washed twice with ethyl acetate (2×10 mL). The combined ethyl acetate layer was dried (Na2SO4), concentrated and the residue was purified by preparative chromatography (10% MeOH/CH2Cl2) to obtain 20 mg (83%) of 5-(3-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (Compound 5).

Workup

  1. customsolvents were removed
  2. custompartitioned between 10 ml of H2O
  3. customThe organic layer was separated
  4. washthe aqueous phase was washed twice with ethyl acetate (2×10 mL)
  5. dry with materialThe combined ethyl acetate layer was dried (Na2SO4)
  6. concentrationconcentrated
  7. customthe residue was purified by preparative chromatography (10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-84c58c45506246f89aed4980ffd8b49f
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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