Lithium Hydroxide → HCID 657065, compound

HRID 2193915Notes

Reaction equation

HRID 2193915 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:8][C:9]=1[N:10]([C:14](=[O:23])[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=1[Cl:22])[CH:11]([CH3:13])[CH3:12])=[O:4].[Li+].[OH-]>C1COCC1.CO.O>[Cl:22][C:16]1[CH:17]=[C:18]([Cl:21])[CH:19]=[CH:20][C:15]=1[C:14]([N:10]([CH:11]([CH3:13])[CH3:12])[C:9]1[CH:8]=[C:7]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[S:6][C:5]=1[C:3]([OH:4])=[O:2])=[O:23]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 16074767HCID 16074767, compound

Product 1

HCID 657065HCID 657065, compound

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

3-[(2,4-Dichloro-benzoyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (3) (345 mg, 0.77 mmol) was dissolved in a mixture of THF-MeOH—H2O (3:2:1) (30 mL) and then 4.6 ml of LiOH 1N was added to it. After 120 min of stirring at room temperature, solvent was removed and then partitioned between 25 ml of H2O, 4 ml of KHSO4 5% and 25 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 175 mg (53%) as a white solid of 3-[(2,4-Dichloro-benzoyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid. NMR 1H (DMSO, 400 MHz): Rotamer 95/05: 7.82 ppm (m, Haro, minor rotamer); 7.69 ppm (d, 2H, Haro); 7.61 ppm (d, 1H, Haro); 7.51-7.37 ppm (m, 4H, Haro); 7.35-7.28 ppm (m, 2H, Haro); 4.89 ppm (hex, 1H, N—CH(CH3), major rotamer); 3.84 ppm (hex, N—CH(CH3), minor rotamer); 1.36 ppm (d, 3H, N—CH(CH3), major rotamer); 1.25 ppm (d, N—CH(CH3), minor rotamer); 1.03 ppm (d, 3H, N—CH(CH3), major rotamer); 0.93 ppm (d, N—CH(CH3), minor rotamere).

Workup

  1. customsolvent was removed
  2. custompartitioned between 25 ml of H2O, 4 ml of KHSO4 5% and 25 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-6df71747ddcd4053a6779cad7ba288dc
Source dataset
uspto-grants-2012_12
Patent number
US08329924B2

Reaction notes

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