Water → 3-[(1-Acetyl-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid

HRID 73192Notes

Reaction equation

HRID 73192 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:8][C:9]=1[N:10]([CH:20]1[CH2:25][CH2:24][N:23]([C:26](=[O:28])[CH3:27])[CH2:22][CH2:21]1)[C:11]([CH:13]1[CH2:18][CH2:17][CH:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].O.[Li+].[OH-]>O1CCOCC1>[C:26]([N:23]1[CH2:22][CH2:21][CH:20]([N:10]([C:11]([CH:13]2[CH2:14][CH2:15][CH:16]([CH3:19])[CH2:17][CH2:18]2)=[O:12])[C:9]2[CH:8]=[C:7]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[S:6][C:5]=2[C:3]([OH:4])=[O:2])[CH2:25][CH2:24]1)(=[O:28])[CH3:27]

Participants

5

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 597522933-[(1-Acetyl-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 103445733-[(1-Acetyl-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acidYield 56%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

3-[(1-Acetyl-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (50 mg, 0.104 mmol) was dissolved in a 4:1 mixture of dioxane:H2O (1 ml) and then LiOH 1N (310 ul, 0.310 mmol) was added. After 5 hours of stirring at room temperature and 4 hours at reflux, solvents were removed and then partitioned between 5 ml of H2O acidified to pH 4 and 5 ml of EtOAc. The organic layer was separated and the aqueous phase was washed twice with ethyl acetate (2×5 mL). The combined ethyl acetate layer was dried (Na2SO4) and concentrated. The residue was purified by preparative chromatography (100/90/16/1 CH2Cl2/CHCl3/MeOH/Et3N) to obtain 27 mg (56%) of 3-[(1-Acetyl-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid (Compound 48).

Workup

  1. temperatureat reflux
  2. customsolvents were removed
  3. custompartitioned between 5 ml of H2O
  4. customThe organic layer was separated
  5. washthe aqueous phase was washed twice with ethyl acetate (2×5 mL)
  6. dry with materialThe combined ethyl acetate layer was dried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was purified by preparative chromatography (100/90/16/1 CH2Cl2/CHCl3/MeOH/Et3N)

Sources & evidence

ORD record
ord-5ac93b4c79ce47f3b9d82d7bf8c7cfb6
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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