Methyl 5-[(3-chlorophenyl)methyl]-4-{2-[(1,1-dimethylethyl)dimethylsilyl]oxyethoxy}thiophene-3-carboxylate → 5-[(3-Chlorophenyl)methyl]4-{2-[(1,1-dimethylethyl)dimethylsilyl]oxyethoxy}thiophene-3-carboxylic acid

HRID 1835170Notes

Reaction equation

HRID 1835170 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]2[S:13][CH:12]=[C:11]([C:14]([O:16]C)=[O:15])[C:10]=2[O:18][CH2:19][CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH:5]=[CH:6][CH:7]=1>[OH-].[Li+].CO.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]2[S:13][CH:12]=[C:11]([C:14]([OH:16])=[O:15])[C:10]=2[O:18][CH2:19][CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 1

HCID 23503266Methyl 5-[(3-chlorophenyl)methyl]-4-{2-[(1,1-dimethylethyl)dimethylsilyl]oxyethoxy}thiophene-3-carboxylate

Product 1

HCID 235032315-[(3-Chlorophenyl)methyl]4-{2-[(1,1-dimethylethyl)dimethylsilyl]oxyethoxy}thiophene-3-carboxylic acidYield 42.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3939Lithium HydroxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 5-[(3-chlorophenyl)methyl]-4-{2-[(1,1-dimethylethyl)dimethylsilyl]oxyethoxy}thiophene-3-carboxylate (10.2 g) was dissolved in a mixture of 1M lithium hydroxide (50 ml), methanol (50 ml) and tetrahydrofuran (150 ml) and stirred for 18 hr. The reaction mixture was concentrated and the residue was partitioned between dichloromethane and 2M hydrochloric acid. The organic layer was collected, dried and filtered. t-Butyl-dimethylsilyl chloride (7 g) and imidazole (3.1 g) were added to the solution and the mixture was stirred for 72 hours. The reaction mixture was concentrated and the residue was dissolved in methanol. Potassium carbonate (5 g) was added to the solution and the suspension was vigorously stirred for 3 minutes, then filtered and concentrated. The residue was dissolved in ethyl acetate, washed with 2M hydrochloric acid, dried, filtered and concentrated. The residue was purified by chromatography, eluting with 10:1:1 isohexane:ethyl acetate:acetic acid, to give the sub-title compound (4.2 g).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between dichloromethane and 2M hydrochloric acid
  3. customThe organic layer was collected
  4. customdried
  5. filtrationfiltered
  6. additiont-Butyl-dimethylsilyl chloride (7 g) and imidazole (3.1 g) were added to the solution
  7. stirringthe mixture was stirred for 72 hours
  8. concentrationThe reaction mixture was concentrated
  9. dissolutionthe residue was dissolved in methanol
  10. additionPotassium carbonate (5 g) was added to the solution
  11. stirringthe suspension was vigorously stirred for 3 minutes
  12. filtrationfiltered
  13. concentrationconcentrated
  14. dissolutionThe residue was dissolved in ethyl acetate
  15. washwashed with 2M hydrochloric acid
  16. customdried
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customThe residue was purified by chromatography
  20. washeluting with 10:1:1 isohexane

Sources & evidence

ORD record
ord-0477a94ef6794d45b557dfe2fe34ff81
Source dataset
uspto-grants-2004_08
Patent number
US06770646B2

Reaction notes

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