Tetrahydrofuran → (6-Bromo-1H-indol-3-yl)acetic acid

HRID 1819678Notes

Reaction equation

HRID 1819678 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=O)[C:12]([OH:14])=[O:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.CC1C=CC(S(NN)(=O)=O)=CC=1.C1COCC1.[BH4-].[Na+]>CO.CCO.O.Cl>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:11][C:12]([OH:14])=[O:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 15303P-ToluenesulfonylhydrazideHCID 4311764Sodium borohydrideHCID 21950065HCID 21950065, compound

Product 1

HCID 22485713(6-Bromo-1H-indol-3-yl)acetic acidYield 2.4%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 18681192Ethanol, mixt. with methanolSolvent

Conditions

Temperature
50 °C

Procedure

Step E (2): To a solution of 2-(6-bromo-1H-indol-3-yl)-2-oxoacetic acid (780 mg, 2.9 mmol) from Step E (1) in MeOH/EtOH (20.0 mL/5.0 mL) was added 4-methylbenzenesulfonohydrazide (1.1 g, 5.8 mmol). The mixture was heated at reflux for 5 h. The solvent was removed. 15 mL of THF and NaBH4 (658 mg, 17.4 mmol) were then added. The reaction mixture was stirred at 50° C. overnight and then at an additional 6 h at 80° C. The reaction mixture was diluted with H2O and 1.0 N HCl and washed with EtOAc. The aqueous layer was concentrated and the residue was purified using reverse phase Prep-HPLC to give 18 mg of the title compound. MS (ESI) (M−H)+=251.98/254.01. 1H-NMR (500 MHz, CD3OD) δ 7.52 (s, 1 H), 7.46 (d, J=8.55 Hz, 1 H), 7.19 (s, 1 H), 7.14 (dd, J=8.55, 1.53 Hz, 1 H), 3.73 (s, 2 H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 5 h
  3. customThe solvent was removed
  4. waitat an additional 6 h at 80° C
  5. washwashed with EtOAc
  6. concentrationThe aqueous layer was concentrated
  7. customthe residue was purified

Sources & evidence

ORD record
ord-b0f2f5b050f3430d9cd24f6c4a76520e
Source dataset
uspto-grants-2009_10
Patent number
US07601751B2

Reaction notes

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