Methanol → Indole

HRID 1095524Notes

Reaction equation

HRID 1095524 reaction equation
N1C=CC=CC=1C[C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1.OC1(CC2C=CC=CN=2)C2C(=CC=CC=2)NC1=O.CO>O1CCCC1>[NH:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:8]=[CH:9]1

Participants

5

Reactant 3

HCID 887MethanolHCID 21756Indole, 3-(2-pyridylmethyl)-HCID 227333-Hydroxy-3-(2-pyridylmethyl)-2-indolinone

Product 1

HCID 798Indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Pyridin-2-ylmethyl-1H-indole (Ind-49) A 2 M solution of borane-dimethyl sulfide complex (20 ml, 40 mmol) was added to a solution of 3-hydroxy-3-pyridin-2-ylmethyl-1,3-dihydroindol-2-one (4.80 g, 20 mmol) in anhydrous tetrahydrofuran (250 ml) and the mixture was stirred at room temperature overnight. Methanol (10 ml) was cautiously added to the reaction mixture and the mixture was concentrated i. vac. Methanol was repeatedly added to the residue, the mixture was in each case concentrated again i. vac., and the residue was taken up in 1N hydrochloric acid. The aqueous suspension was extracted with ethyl acetate (2×40 ml). The aqueous phase was adjusted to pH 10 with saturated potassium carbonate solution and extracted with ethyl acetate (3×30 ml). The combined organic phases were dried with sodium sulfate and concentrated i. vac. The crude product (4.0 g) was purified by flash chromatography (400 g, 20×7.6 cm) first with ethyl acetate/cyclohexane (2:1) and then chloroform.

Workup

  1. concentrationthe mixture was concentrated i
  2. additionMethanol was repeatedly added to the residue
  3. concentrationconcentrated again
  4. extractionThe aqueous suspension was extracted with ethyl acetate (2×40 ml)
  5. extractionextracted with ethyl acetate (3×30 ml)
  6. dry with materialThe combined organic phases were dried with sodium sulfate
  7. concentrationconcentrated i
  8. customThe crude product (4.0 g) was purified by flash chromatography (400 g, 20×7.6 cm) first with ethyl acetate/cyclohexane (2:1)

Sources & evidence

ORD record
ord-dfbb2b764b394e3880130005f8f95d40
Source dataset
uspto-grants-2012_03
Patent number
US08138187B2

Reaction notes

Loading…