Lithium hydroxide, monohydrate → 5-(3-Fluoro-phenyl)-3-[(2-hydroxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-thiophene-2-carboxylic acid

HRID 749336Notes

Reaction equation

HRID 749336 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=2)=[CH:8][C:9]=1[N:10]([C:14]([CH:16]1[CH2:21][CH2:20][CH:19]([CH3:22])[CH2:18][CH:17]1[O:23]C(=O)C)=[O:15])[CH:11]([CH3:13])[CH3:12])=[O:4].O[Li].O>C1COCC1.CO.O>[F:33][C:29]1[CH:28]=[C:27]([C:7]2[S:6][C:5]([C:3]([OH:4])=[O:2])=[C:9]([N:10]([C:14]([CH:16]3[CH2:21][CH2:20][CH:19]([CH3:22])[CH2:18][CH:17]3[OH:23])=[O:15])[CH:11]([CH3:12])[CH3:13])[CH:8]=2)[CH:32]=[CH:31][CH:30]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 597523393-[(2-Acetoxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-(3-fluoro-phenyl)-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 100707145-(3-Fluoro-phenyl)-3-[(2-hydroxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-thiophene-2-carboxylic acidYield 58%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

3[(2-Acetoxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-(3-fluoro-phenyl)-thi-ophene-2-carboxylic acid methyl ester (30 mg, 0.063 mmol) was taken in a mixture of THF:MeOH:H2O (3:2:1, 2 mL) and then added 1N aqueous solution of LiOH.H2O (0.38 mL, 0.380 mmol). The reaction mixture was stirred at room temperature for 12 h. Solvents were removed and the residue was partitioned between water and ethyl acetate. The aqueous layer was acidified using 10% KHSO4 solution. The organic layer was separated, dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography using chloroform and methanol (8:2) to obtain 5-(3-fluoro-phenyl)-3-[(2-hydroxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-thiophene-2-carboxylic acid (Compound 44) (15 mg, 58%) as a white solid with two rotamers. 1H NMR (CDCl3, 400 MHz): δ7.50-7.25 (m, 3H), 7.06 (m, 2H), 6.25 (bs, 1H), 5.25 (s, 1H, minor), 4.87 (s, 1H, major), 4.13 (s, 1H, major), 3.87 (s, 1H, minor), 2.38-0.45 (m, 17H). ESI− (M−H): 418.

Workup

  1. customSolvents were removed
  2. customthe residue was partitioned between water and ethyl acetate
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-cb7a8ec963a648b78f2d4ca13d70def1
Source dataset
uspto-grants-2008_07
Patent number
US07402608B2

Reaction notes

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