Sodium hydride → HCID 10358416, compound

HRID 1918828Notes

Reaction equation

HRID 1918828 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:16]2[NH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]=2[CH2:7][CH2:6][NH:5]1.[CH3:17][Si:18]([CH3:25])([CH3:24])[CH2:19][CH2:20][O:21][CH2:22]Cl>>[CH3:17][Si:18]([CH3:25])([CH3:24])[CH2:19][CH2:20][O:21][CH2:22][N:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]2[CH2:7][CH2:6][NH:5][C:4](=[O:3])[C:16]1=2

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 873712,3,4,9-Tetrahydro-1H-pyrido(3,4-b)indol-1-oneHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether

Product 1

HCID 10358416HCID 10358416, compoundYield 57%

Conditions

Temperature
0 °C

Procedure

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with anhydrous DMF (4 mL) and a 60% dispersion of sodium hydride in mineral oil (181 mg, 4.52 mmol) and the reaction mixture was cooled to 0° C. 1,2,3,4-tetrahydro-1-oxo-beta-carboline (841 mg, 4.52 mmol) was added, and the reaction was stirred at 0° C. for 15 min. After this time, 2-(trimethylsilyl)ethoxymethyl chloride (829 mg, 4.97 mmol) was added, and the reaction was stirred at 0° C. for 1 h. The reaction mixture was then partitioned between water (10 mL) and ethyl acetate (20 mL). The layers were separated, and the aqueous phase was extracted with ethyl acetate (2×10 mL). The organic extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography to afford 117a in 57% yield (818 mg) as a colorless oil: 1H NMR (500 MHz, CDCl3) d 7.67 (d, 1H, J=8.0 Hz), 7.65 (d, 1H, J=8.0 Hz), 7.46 (t, 1H, J=8.0 Hz), 7.27 (t, 1H, J=8.0 Hz), 6.14 (s, 2H), 5.72 (br s, 1H), 3.75 (t, 2H, J=7.0 Hz), 3.66 (t, 2H, J=8.0 Hz), 3.14 (t, 2H, J=7.0 Hz), 0.96 (t, 2H, J=8.0 Hz), −0.25 (s, 9H).

Workup

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customwas purged with nitrogen
  3. additioncharged with anhydrous DMF (4 mL)
  4. stirringthe reaction was stirred at 0° C. for 1 h
  5. customThe reaction mixture was then partitioned between water (10 mL) and ethyl acetate (20 mL)
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with ethyl acetate (2×10 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-95d17890e16f43eabba91e0ccb903b41
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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