3-Bromopropionaldehyde dimethylacetal → HCID 66899269, compound

HRID 2168486Notes

Reaction equation

HRID 2168486 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([O:12][CH3:13])=[O:11])[CH:3]=[CH:2]1.CC(C)([O-])C.[K+].Br[CH2:21][CH2:22][CH:23]([O:26][CH3:27])[O:24][CH3:25]>CS(C)=O.[I-].[K+]>[CH3:25][O:24][CH:23]([O:26][CH3:27])[CH2:22][CH2:21][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([O:12][CH3:13])=[O:11])[CH:3]=[CH:2]1

Participants

6

Reactant 3

HCID 1189323-Bromopropionaldehyde dimethylacetalHCID 676694Methyl indole-7-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 66899269HCID 66899269, compoundYield 92.1%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a stirred solution of methyl 1H-indole-7-carboxylate (3.3 g, 18.8 mmol) in DMSO (18 mL) was added potassium tert-butoxide (2.1 g, 18.8 mmol) in portions. After stirring at room temperature for 1 h, a solution of 3-bromo-1,1-dimethoxypropane (10 g, 54.6 mmol) and potassium iodide (188 mg, 1.1 mmol) in DMSO (15 mL) was added and the mixture was stirred for 15 h. The reaction was quenched with saturated aqueous ammonium chloride and adjusted to pH 6. The aqueous phase was extracted with ethyl acetate (3×) and the combined extracts were washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 90:10 hexanes/ethyl acetate) to give methyl 1-(3,3-dimethoxypropyl)-1H-indole-7-carboxylate (4.8 g, 92%) as a light yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.79 (d, J=7.5 Hz, 1H), 7.68 (d, J=7.5 Hz, 1H), 7.12 (d, J=3.0 Hz, 1H), 7.11 (t, J=7.5 Hz, 1H), 6.56 (d, J=3.5 Hz, 1H), 4.49 (t, J=7.0 Hz, 2H), 4.09 (t, J=6.0 Hz, 1H), 3.97 (s, 3H), 3.25 (s, 6H), 1.97 (q, J=6.0 Hz, 2H).

Workup

  1. stirringthe mixture was stirred for 15 h
  2. customThe reaction was quenched with saturated aqueous ammonium chloride
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  4. washthe combined extracts were washed with saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by column chromatography (silica gel, 90:10 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-eb812d6db03447df93b5d5eb1c99ada9
Source dataset
uspto-grants-2015_06
Patent number
US09045501B2

Reaction notes

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