Methyl iodide → HCID 86701549, compound

HRID 2173981Notes

Reaction equation

HRID 2173981 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:29][OH:30])[C:5]([CH2:21][O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)=[C:6]2[C:10]=1[N:9]([S:11]([C:14]1[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=1)(=[O:13])=[O:12])[CH:8]=[CH:7]2.[H-].[Na+].[CH3:33]I>CN(C=O)C>[CH3:33][O:30][CH2:29][C:4]1[C:5]([CH2:21][O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)=[C:6]2[C:10](=[C:2]([CH3:1])[CH:3]=1)[N:9]([S:11]([C:14]1[CH:15]=[CH:16][C:17]([CH3:18])=[CH:19][CH:20]=1)(=[O:13])=[O:12])[CH:8]=[CH:7]2

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86701545HCID 86701545, compound

Product 1

HCID 86701549HCID 86701549, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (±)-(7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indol-5-yl)methanol (Example 52-C) (170 mg, 0.40 mmol) in DMF (1 mL) was added NaH (31.7 mg, 60% in mineral oil, 0.79 mmol) at room temperature, and then the mixture was stirred for 10 min. To the mixture was added MeI (25 uL, 0.40 mmol) at room temperature, and then the mixture was stirred for 2.5 h. The reaction was quenched by half saturated aqueous solution of KHSO4, and diluted with EtOAc. The bi-layer was partitioned. The organic phase was washed successively H2O and brine, dried over Na2SO4, and then filtered. Concentration of the filtrate gave the title compound, without need of any further purification. 1H NMR (400 MHz, DMSO-d6) δ 7.86 (d, J=3.79 Hz, 1H), 7.62 (d, J=8.34 Hz, 2H), 7.39 (d, J=8.34 Hz, 2H), 7.08 (s, 1H), 6.99 (d, J=3.79 Hz, 1H), 4.87 (d, J=11.37 Hz, 1H), 4.67 (d, J=11.37 Hz, 1H), 4.60-4.64 (m, 1H), 4.44-4.54 (m, 2H), 3.73-3.86 (m, 1H), 3.41-3.52 (m, 1H), 3.30 (s, 3H), 2.47 (s, 3H), 2.34 (s, 3H), 1.51-1.78 (m, 2H), 1.34-1.51 (m, 4H).

Workup

  1. stirringthe mixture was stirred for 2.5 h
  2. customThe reaction was quenched by half saturated aqueous solution of KHSO4
  3. additiondiluted with EtOAc
  4. customThe bi-layer was partitioned
  5. washThe organic phase was washed successively H2O and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered

Sources & evidence

ORD record
ord-5ff277a576aa41c4a5449175b7f3982e
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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