Lithium Hydroxide → HCID 178434885, compound

HRID 73224Notes

Reaction equation

HRID 73224 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:8][C:9]=1[N:10]([CH:20]1[CH2:25][CH2:24][C:23]([OH:27])([CH3:26])[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].[OH-].[Li+]>O1CCCC1.O.CO>[OH:27][C:23]1([CH3:26])[CH2:22][CH2:21][CH:20]([N:10]([C:11]([C@H:13]2[CH2:14][CH2:15][C@@H:16]([CH3:19])[CH2:17][CH2:18]2)=[O:12])[C:9]2[CH:8]=[C:7]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[S:6][C:5]=2[C:3]([OH:4])=[O:2])[CH2:25][CH2:24]1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 178499266HCID 178499266, compound

Product 1

HCID 178434885HCID 178434885, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of cis-3-[(4-Hydroxy-4-methyl-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (70.0 mg, 0.149 mmol, 1 eq) in tetrahydrofuran (1 mL), water (0.5 mL) and methanol (0.5 mL) was added lithium hydroxide (19.0 mg, 0.447 mmol, 3 eq). The resulting mixture was stirred 3 h at room temperature and was then extracted with ether (2×10 mL). Aqueous phase was separated and combined organic phases were discarded. Aqueous phase was acidified to pH 1 and extracted with dichloromethane (3×30 mL). Organic phases of dichloromethane were combined, dried over sodium sulfate and concentrated. The crude was purified by chromatography (10% methanol/dichloromethane) to give 50 mg (74%) of cis-3-[(4-Hydroxy-4-methyl-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid. NMR 1H (CDCl3, 400 MHz): 7.60 ppm (d, 2H); 7.39 ppm (m, 3H); 7.03 ppm (s, 1H); 4.51 ppm (bs, 2H); 2.00 ppm (m, 1H); 1.80-1.20 ppm (m, 15H); 1.12 ppm (s, 3H); 0.71 ppm (d, 3H); 0.60 ppm (m, 2H).

Workup

  1. extractionwas then extracted with ether (2×10 mL)
  2. customAqueous phase was separated
  3. extractionextracted with dichloromethane (3×30 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude was purified by chromatography (10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-1314403b3a5a4288a82faab7702ebaa0
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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