Lithium Hydroxide → (1R,2S,4R)-3-[Isopropyl-(2-hydroxy-4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid

HRID 1015661Notes

Reaction equation

HRID 1015661 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([CH:24]([CH3:26])[CH3:25])[C:11]([C@@H:13]1[CH2:18][CH2:17][C@@H:16]([CH3:19])[CH2:15][C@@H:14]1[O:20]C(=O)C)=[O:12])=[O:4].[Li+].[OH-]>O1CCOCC1.O>[CH:24]([N:10]([C:11]([C@@H:13]1[CH2:18][CH2:17][C@@H:16]([CH3:19])[CH2:15][C@@H:14]1[OH:20])=[O:12])[C:9]1[CH:8]=[C:7]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[S:6][C:5]=1[C:3]([OH:4])=[O:2])([CH3:26])[CH3:25]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67299228HCID 67299228, compound

Product 1

HCID 59997623(1R,2S,4R)-3-[Isopropyl-(2-hydroxy-4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acidYield 29%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
50 °C

Procedure

(1R,2S,4R)-3-[Isopropyl-(2-Acetoxy-4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (36 mg, 0.17 mmol) was dissolved in a mixture of dioxane:H2O (4:1) (700 μl) and then 470 μl of LiOH 1N was added to it. After 3 h at 50° C. the reaction mixture was cooled to room temperature and the solvents were removed. The residue was then partitioned between 10 ml of H2O acidified to pH 4 and 10 ml of EtOAc. The organic layer was separated and the aqueous phase was washed with ethyl acetate (2×10 ml). The combined ethyl acetate layers were dried (Na2SO4), concentrated and the residue was purified by preparative chromatography to obtain 9 mg (29%) of (1R,2S,4R)-3-[Isopropyl-(2-hydroxy-4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid. NMR 1H (CDCl3, 400 MHz): 3:2 mixture of rotamers. 7.76-7.73 ppm (m, 2H, Haro); 7.50-7.38 ppm (m, 3H, Haro); 7.36 ppm (s, 1H, Haro); 4.93-4.87 ppm (m, 1H); 4.25 ppm (s, 0.70H, major rotamer); 3.97 ppm (s, 0.3H, minor rotamer); 2.35-2.28 ppm (m, 1H); 1.99-1.53 ppm (m, 5H); 1.28 ppm (d, 0.6H, minor rotamer); 1.25 ppm (d, 1,4H, major rotamer); 1.06-1.03 ppm (m, 3H), 0.96-0.72 ppm (m, 1H); 0.79 ppm (d, 3H); 0.67-0.56 ppm (m, 1H).

Workup

  1. customthe solvents were removed
  2. customThe residue was then partitioned between 10 ml of H2O
  3. customThe organic layer was separated
  4. washthe aqueous phase was washed with ethyl acetate (2×10 ml)
  5. dry with materialThe combined ethyl acetate layers were dried (Na2SO4)
  6. concentrationconcentrated
  7. customthe residue was purified by preparative chromatography

Sources & evidence

ORD record
ord-f2daf602faa4438e8911850304d8ddc8
Source dataset
uspto-grants-2011_07
Patent number
US07985769B2

Reaction notes

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