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

HRID 749336ノート

反応式

HRID 749336 の反応式
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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 21892291Methanol tetrahydrofuran water溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-cb7a8ec963a648b78f2d4ca13d70def1
出典データセット
uspto-grants-2008_07
特許番号
US07402608B2

反応ノート

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