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

HRID 73167Notes

Reaction equation

HRID 73167 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][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][C:16]([CH3:19])=[CH:15][CH2:14]1)=[O:12])=[O:4].O[Li].O>C1COCC1.CO.O>[F:29][C:26]1[CH:25]=[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][C:16]([CH3:19])=[CH:15][CH2:14]3)=[O:12])[CH:8]=2)=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 597522855-(4-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 104087565-(4-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acidYield 23%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
50 °C

Procedure

5-(4-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohex-3-enecarbo-nyl)-amino]-thiophene-2-carboxylic acid methyl ester (0.140 g, 0.34 mmol) was taken in a mixture of THF:MeOH:H2O (3:2:1, 10 mL) and then added 1N aqueous solution of LiOH.H2O (2.1 mL, 2.04 mmol). The reaction mixture was stirred at 50° C. for 1 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 preparative TLC using dicholomethane:methanol (9:1) to obtain 5-(4-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid (compound 53) (31 mg, 23%). 1H NMR (CDCl3, 400 MHz): δ 7.81 (m, 2H), 7.43 (d, 1H), 7.28 (m, 2H), 5.38-5.16 (m, 1H), 4.72 (m, 1H), 2.20 (d, 2H), 1.95-1.20 (m, 8H), 1.12 (m, 3H), 0.90 (d, 3H).

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 preparative TLC

Sources & evidence

ORD record
ord-f9711ebe6b184a1bbfc3c25cf15b119f
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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