Hydrochloric Acid → 5-fluoro-1-benzothiophene-2-carboxylic acid

HRID 1479913Notes

Reaction equation

HRID 1479913 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][C:5]2[S:6][C:7]([C:9]([O:11]CC)=[O:10])=[CH:8][C:4]=2[CH:3]=1.[Li+].[OH-].CO.Cl>C1COCC1.O>[F:1][C:2]1[CH:15]=[CH:14][C:5]2[S:6][C:7]([C:9]([OH:11])=[O:10])=[CH:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 23261724Ethyl 5-fluorobenzo[b]thiophene-2-carboxylate

Product 1

HCID 9014395-fluoro-1-benzothiophene-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 8 (246.68 mg, 1.1 mmol) and LiOH (75.9 mg, 3.3 mmol) in THF (9 mL) was added MeOH (1 mL) and H2O (3 mL), stirred at room temperature for 6 h. Then HCl (1 M) was added to the reaction mixture to pH=4, and extracted with EtOAc (3×15 mL), wash with H2O (3×20 mL). The organic extracts were dried with Na2SO4 and concentrated under reduced pressure. Purified by flash chromatography on silica gel, using ethyl acetate/hexane (4:1) as eluent, give 8-acid as white powder; (212.79 mg, 98.6%). 1H-NMR (300 MHz, acetone-d6): δ 8.14 (s, 1H), 8.10-8.05 (m, 1H), 7.80-7.76 (m, 1H), 7.41-7.34 (m, 1H). 13C NMR (300 MHz, acetone-d6): δ 162.52, 159.31, 140.12, 137.78, 130.11, 124.65, 116.10, 110.66.

Workup

  1. extractionextracted with EtOAc (3×15 mL)
  2. washwash with H2O (3×20 mL)
  3. dry with materialThe organic extracts were dried with Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customPurified by flash chromatography on silica gel
  6. customgive 8-acid as white powder

Sources & evidence

ORD record
ord-2a21766f6d434d638663544fabf9a0ef
Source dataset
uspto-grants-2016_08
Patent number
US09409880B2

Reaction notes

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