2-[(2-Chloro-4-methyl-5-nitrophenyl)methoxy]tetrahydro-2H-pyran → 5-Chloro-7-methyl-4-[[(tetrahydro-2H-pyran-2-yl)oxy]methyl]-1H-indole

HRID 2173967Notes

Reaction equation

HRID 2173967 reaction equation
[CH:1]([Mg]Br)=[CH2:2].[Cl:5][C:6]1[CH:19]=[C:18]([CH3:20])[C:17]([N+:21]([O-])=O)=[CH:16][C:7]=1[CH2:8][O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1>C1COCC1>[Cl:5][C:6]1[C:7]([CH2:8][O:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)=[C:16]2[C:17](=[C:18]([CH3:20])[CH:19]=1)[NH:21][CH:2]=[CH:1]2

Participants

4

Reactant 2

HCID 867015352-[(2-Chloro-4-methyl-5-nitrophenyl)methoxy]tetrahydro-2H-pyranHCID 178418507HCID 178418507, compound

Product 1

HCID 867015365-Chloro-7-methyl-4-[[(tetrahydro-2H-pyran-2-yl)oxy]methyl]-1H-indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of vinylmagnesium bromide (1M in THF, 200 mL, 200 mmol) was added dropwise (±)-2-((2-chloro-4-methyl-5-nitrobenzyl)oxy)tetrahydro-2H-pyran (14 g, 49.0 mmol) in THF (40 mL) below −20° C. After completion of the addition, the flask was removed from the ice bath with stirring. After 2 h, the reaction mixture was cooled to below −20° C. The reaction was quenched with MeOH with maintaining the temperature below 0° C. The mixture was diluted with CH2Cl2 and H2O. The mixture was filtered through Celite®. The Celite® cake was washed with CH2Cl2. The layers were separated and the organic phase was washed with H2O and brine, dried over Na2SO4, and then filtered. Concentration of the filtrate gave the title compound, which was used in the next reaction without any further purification. For an analytical purpose, the crude was purified by SiO2 column chromatography [heptane/(30% EtOAc in CH2Cl2)]=69/31] to afford the title compound. 1H NMR (400 MHz, ACETONITRILE-d3) δ 9.43 (br. s., 1H), 7.29-7.36 (m, 1H), 6.99 (s, 1H), 6.58-6.70 (m, 1H), 5.05 (d, J=11.12 Hz, 1H), 4.84 (d, J=11.10 Hz, 1H), 4.67-4.77 (m, 1H), 3.89-4.03 (m, 1H), 3.46-3.60 (m, 1H), 2.47 (s, 3H), 1.59-1.75 (m, 2H), 1.43-1.59 (m, 4H)

Workup

  1. additionAfter completion of the addition
  2. customthe flask was removed from the ice bath
  3. temperaturethe reaction mixture was cooled to below −20° C
  4. customThe reaction was quenched with MeOH
  5. temperaturewith maintaining the temperature below 0° C
  6. additionThe mixture was diluted with CH2Cl2 and H2O
  7. filtrationThe mixture was filtered through Celite®
  8. washThe Celite® cake was washed with CH2Cl2
  9. customThe layers were separated
  10. washthe organic phase was washed with H2O and brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered

Sources & evidence

ORD record
ord-72dde715c72e421abf3299a8a764ca01
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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