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

HRID 1807964Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1807964
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

Komponenten

4

Edukt 2

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21892291Methanol tetrahydrofuran waterLösungsmittel

Versuchsvorschrift

3-[(2-Acetoxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-(3-fluoro-phenyl)-thiophene-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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-c5f6277aa36d4851920a72d59ce34d26
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08357718B2

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