Lithium hydroxide, monohydrate → 3-[Isopropyl-(4-methylene-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid

HRID 73164Notes

Reaction equation

HRID 73164 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:23]2[CH:28]=[CH:27][CH:26]=[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](=[CH2:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].O[Li].O>C1COCC1.CO.O>[CH:20]([N:10]([C:11]([CH:13]1[CH2:14][CH2:15][C:16](=[CH2:19])[CH2:17][CH2:18]1)=[O:12])[C:9]1[CH:8]=[C:7]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[S:6][C:5]=1[C:3]([OH:4])=[O:2])([CH3:22])[CH3:21]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 597522963-[Isopropyl-(4-methylene-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 103625563-[Isopropyl-(4-methylene-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acidYield 52%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

3-[Isopropyl-(4-methylene-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (50 mg, 0.126 mmol) was taken in a mixture of THF:MeOH:H2O (3:2:1, 3 mL) and then 1N aqueous solution of LiOH.H2O (0.8 mL, 0.800 mmol) was added. 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 3-[Isopropyl-(4-methylene-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid (compound 28) (25 mg, 52%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ7.61 (d, J=7 Hz, 2H), 7.40-7.38 (m, 3H), 7.04 (s, 1H), 4.92 (m, 1H), 4.50 (d, J=7.6 Hz, 2H), 2.21-1.43 (m, 9H), 1.15 (bd, 3H), 0.93 (bd, 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 silica gel column chromatography

Sources & evidence

ORD record
ord-9ca6fd4e0f5541d9829e5158455b9fd3
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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