Lithium Hydroxide → 3-[Tert-butyl-(2,4-dichlorobenzoyl)amino]-5-phenyl-thiophene-2-carboxylic acid

HRID 2193921Notes

Reaction equation

HRID 2193921 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:8][C:9]=1[N:10]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:11](=[O:20])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=1[Cl:19])=[O:4].[Li+].[OH-]>C1COCC1.CO.O>[C:21]([N:10]([C:11](=[O:20])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=1[Cl:19])[C:9]1[CH:8]=[C:7]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[S:6][C:5]=1[C:3]([OH:4])=[O:2])([CH3:24])([CH3:22])[CH3:23]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 207757533-[tert-Butyl-(2,4-dichloro-benzoyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 160748013-[Tert-butyl-(2,4-dichlorobenzoyl)amino]-5-phenyl-thiophene-2-carboxylic acidYield 29.7%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

3-[tert-Butyl-(2,4-dichloro-benzoyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (112 mg, 0.24 mmol) was dissolved in a mixture of THF-MeOH—H2O (3:2:1) (15 mL) and then 1.5 ml of LiOH 1N was added to it. After 3 h of stirring at room temperature, solvent was removed and then partitioned between 15 ml of H2O, 4 ml of KHSO4 5% and 15 ml of EtOAc. The organic layer was separated and the aqueous phase was washed twice with ethyl acetate (2×10 mL). The combined ethyl acetate layer was dried (MgSO4), concentrated and the residue was purified by preparative chromatography (10% MeOH/CH2Cl2) to obtain 32 mg (29%) of 3-[tert-Butyl-(2,4-dichloro-benzoyl)-amino]-5-phenyl-thiophene-2-carboxylic acid. NMR 1H (DMSO, 400 MHz): 7.62 ppm (d, 2H, Haro); 7.44-7.34 ppm (m, 4H, Haro); 7.32-7.12 ppm (m, 3H, Haro); 2.48 ppm (s, 9H).

Workup

  1. customsolvent was removed
  2. custompartitioned between 15 ml of H2O, 4 ml of KHSO4 5% and 15 ml of EtOAc
  3. customThe organic layer was separated
  4. washthe aqueous phase was washed twice with ethyl acetate (2×10 mL)
  5. dry with materialThe combined ethyl acetate layer was dried (MgSO4)
  6. concentrationconcentrated
  7. customthe residue was purified by preparative chromatography (10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-8c2c62726fbc42ff93eef786fa2f9a9c
Source dataset
uspto-grants-2012_12
Patent number
US08329924B2

Reaction notes

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