Hydrochloric Acid → 2-Hydroxy-2-(4-hydroxybenzo[b]thiophen-7-yl)acetic acid

HRID 2177198Notes

Reaction equation

HRID 2177198 reaction equation
[S:1]1[C:5]2=[CH:6][CH:7]=[CH:8][C:9]([OH:10])=[C:4]2[CH:3]=[CH:2]1.[OH-].[K+].[O:13]=[CH:14][C:15]([OH:17])=[O:16].Cl.C(N(CCCC)CCCC)CCC>O.COC(C)(C)C>[OH:13][CH:14]([C:6]1[C:5]2[S:1][CH:2]=[CH:3][C:4]=2[C:9]([OH:10])=[CH:8][CH:7]=1)[C:15]([OH:17])=[O:16]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 760Glyoxylic Acid2×HCID 7622TributylamineHCID 14797Potassium HydroxideHCID 19217Benzo(b)thiophen-4-ol

Product 1

HCID 111836762-Hydroxy-2-(4-hydroxybenzo[b]thiophen-7-yl)acetic acidYield 111.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolvent2×

Procedure

Into a 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 1-benzothiophen-4-ol (1.0 g, 6.32 mmol, 1.00 equiv, 95%), potassium hydroxide (821 mg, 1.46 mmol, 2.20 equiv, 10%). This was followed by the addition of 2-oxoacetic acid (592 mg, 4.00 mmol, 1.20 equiv) at 0-5° C. with 30 min. If necessary, more 2-oxoacetic acid is added such that the pH of the solution at the end of the addition was 11.5. After stirring for 3 h at 0-5 degree C. 20 mL of tert-butyl methyl ether were added to the reaction mixture followed by HCl(25%) solution in water such that the pH was 7. The biphasic mixture was filtered through Speedex, then HCl (25%) solution in water were added to the aqueous phase such that the pH was 2.0. After addition of tert-butyl methyl ether (3*20 mL), the organic phase was separated at 25° C., and 50 mL acetonitrile was added to organic phase. To the resulting clear solution was added portions wise at 20-30° C., a solution of tributylamine (1.23 g, 1.00 equiv) in 20 mL of tert-butyl methyl ether under seeding with crystals of the product. The resulting suspension was stirred over night at 20-30 degree C., and then filtered off. The filter cake was dried oven at 60° C. The result afford (1.0 g, 63%) of 2-hydroxy-2-(4-hydroxy-1-benzothiophen-7-yl)acetic acid as gray solid.

Workup

  1. customInto a 100-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. filtrationThe biphasic mixture was filtered through Speedex
  4. additionHCl (25%) solution in water were added to the aqueous phase such that the pH was 2.0
  5. additionAfter addition of tert-butyl methyl ether (3*20 mL)
  6. customthe organic phase was separated at 25° C.
  7. addition50 mL acetonitrile was added to organic phase
  8. additionTo the resulting clear solution was added portions wise at 20-30° C.
  9. stirringThe resulting suspension was stirred over night at 20-30 degree C
  10. filtration, and then filtered off
  11. customThe filter cake was dried oven at 60° C

Sources & evidence

ORD record
ord-f0c268f26c0046ca95549107fbfd466d
Source dataset
uspto-grants-2015_06
Patent number
US09067898B1

Reaction notes

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