Isopropanol → HCID 68945853, compound

HRID 2377137Notes

Reaction equation

HRID 2377137 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][CH3:11])[CH:3]=1.C([Li])CCC.CON(C)[C:20]([C:22]1[CH:30]=[C:29]2[C:25]([CH:26]=[CH:27][NH:28]2)=[CH:24][CH:23]=1)=[O:21].C(O)(C)C>C1COCC1.O>[CH3:11][O:10][C:4]1[CH:3]=[C:2]([C:20]([C:22]2[CH:30]=[C:29]3[C:25]([CH:26]=[CH:27][NH:28]3)=[CH:24][CH:23]=2)=[O:21])[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=1

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 6391871-Bromo-3,5-dimethoxybenzeneHCID 3616760HCID 3616760, compoundHCID 178418339Butyllithium

Product 1

HCID 68945853HCID 68945853, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1-bromo-3,5-dimethoxybenzene (12.86 g, 59.3 mmol) in THF (60 mL) was cooled to −78° C., evacuated and refilled with nitrogen for 10 cycles. To this clear solution was slowly added n-butyllithium (23.7 mL, 59.3 mmol) and stirred for 30 min. Then a mixture of 1H-Indole-6-carboxylic acid methoxy-methyl-amide (5.50 g, 26.9 mmol) in THF (40 mL) was added and stirred for 3 h at −78° C. The mixture was quenched with isopropanol (12.5 mL, 162 mmol) and added water (40 mL). It was extracted with ether (3×50 mL), washed with water (2×50 mL), dried and concentrated to an oil, which was purified by flash column chromatography (EtOAc/Hexane) to give (3,5-dimethoxy-phenyl)-(1H-indol-6-yl)-methanone as an oil (3.70 g, 49% yield). The product was used in the next step without further purification.

Workup

  1. customevacuated
  2. additionrefilled with nitrogen for 10 cycles
  3. additionwas added
  4. stirringstirred for 3 h at −78° C
  5. extractionIt was extracted with ether (3×50 mL)
  6. washwashed with water (2×50 mL)
  7. customdried
  8. concentrationconcentrated to an oil, which
  9. customwas purified by flash column chromatography (EtOAc/Hexane)

Sources & evidence

ORD record
ord-02569cfee98649469c8545be3e67f2e3
Source dataset
uspto-grants-2008_12
Patent number
US07468446B2

Reaction notes

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