Sodium Hydroxide → HCID 17836490, compound

HRID 348509Notes

Reaction equation

HRID 348509 reaction equation
[C:1]([C:3]1[C:4]2[C:16]([CH3:17])=[CH:15][CH:14]=[CH:13][C:5]=2[S:6][C:7]=1[C:8]([O:10]CC)=[O:9])#[N:2].[OH-].[Na+]>CO.C1COCC1.O>[C:1]([C:3]1[C:4]2[C:16]([CH3:17])=[CH:15][CH:14]=[CH:13][C:5]=2[S:6][C:7]=1[C:8]([OH:10])=[O:9])#[N:2]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 17836478HCID 17836478, compound

Product 1

HCID 17836490HCID 17836490, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

15.59 g (63.6 mmol) of the 3-cyano-2-ethoxycarbonyl-4-methylbenzo[b]thiophene obtained in Step 3 were dissolved in a mixture of methanol (150 ml), THF (150 ml) and water (150 ml) followed by the addition of 30 ml of 5 M aqueous sodium hydroxide solution and stirring for 2 hours at room temperature. After concentrating the solvent under reduced pressure, the pH was lowered to 4 by addition of 1 M hydrochloric acid and, after extracting with ethyl acetate and washing the organic phase with water, it was dried with magnesium sulfate. The solvent was then concentrated under reduced pressure to obtain 3-cyano-2-carboxy-4-methylbenzo[b]thiophene. This and 1.27 g (20 mmol) of copper powder were added to 18 ml of quinoline followed by stirring for 2 hours at 150° C. After cooling the reaction solution, it was filtered with Celite and the pH of the filtrate was lowered to 3 by addition of hydrochloric acid to transfer the quinoline as the solvent to the aqueous phase followed by extraction with ethyl acetate. After washing the organic phase with water, it was dried with magnesium sulfate and the solvent was concentrated under reduced pressure. The residue was then purified by silica gel column chromatography (hexane:ethyl acetate=20:1) to obtain 9.10 g (52.6 mmol) of the target compound (yield of the two steps: 83%).

Workup

  1. concentrationAfter concentrating the solvent under reduced pressure
  2. additionthe pH was lowered to 4 by addition of 1 M hydrochloric acid
  3. extractionafter extracting with ethyl acetate
  4. washwashing the organic phase with water, it
  5. dry with materialwas dried with magnesium sulfate
  6. concentrationThe solvent was then concentrated under reduced pressure

Sources & evidence

ORD record
ord-14a5e1d818234927a447594a1c1d9e65
Source dataset
uspto-grants-2007_02
Patent number
US07176320B2

Reaction notes

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