Methyl iodide → HCID 86301332, compound

HRID 513935Notes

Reaction equation

HRID 513935 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:21]=[CH:22][CH:23]=1)[CH2:7][O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[C:14]([CH2:19][OH:20])[CH:15]=[N:16]2)=[CH:11][CH:10]=1.[CH3:24]I>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]([CH:21]=[CH:22][CH:23]=1)[CH2:7][O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[C:14]([CH2:19][O:20][CH3:24])[CH:15]=[N:16]2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86301179HCID 86301179, compound

Product 1

HCID 86301332HCID 86301332, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a cooled solution of NaH (60% in mineral oil, 12 mg, 0.3 mmol) in DMF (0.5 mL) under an atmosphere of nitrogen, was added a solution of (7-((3-chlorobenzyl)oxy)quinolin-3-yl)methanol (Example 35, 30 mg, 0.10 mmol) in DMF (0.5 mL). The reaction was stirred for 10 minutes. Methyl iodide (0.019 mL, 0.3 mmol) was added and the reaction was stirred for an additional 25 minutes at 0° C. before being quenched with a sat. NH4Cl (aq.) solution. The aqueous layer was extracted with EtOAc. The organic layers were combined and concentrated onto silica. Purification (FCC, SiO2, 0-60%, EtOAc/hexanes) afforded the title compound as a white solid (19 mg, 61%). 1H NMR (400 MHz, CDCl3) δ 8.81 (d, J=2.0 Hz, 1H), 8.05 (d, J=1.6 Hz, 1H), 7.73 (d, J=8.6 Hz, 1H), 7.50 (s, 1H), 7.46 (d, J=2.7 Hz, 1H), 7.39-7.27 (m, 4H), 5.19 (s, 2H), 4.62 (s, 2H), 3.45 (s, 3H). [M+H]=314.2.

Workup

  1. stirringthe reaction was stirred for an additional 25 minutes at 0° C.
  2. custombefore being quenched with a sat. NH4Cl (aq.) solution
  3. extractionThe aqueous layer was extracted with EtOAc
  4. concentrationconcentrated onto silica
  5. customPurification (FCC, SiO2, 0-60%, EtOAc/hexanes)

Sources & evidence

ORD record
ord-5ab29e3acefa4abb987565bb5008e49c
Source dataset
uspto-grants-2015_08
Patent number
US09102674B2

Reaction notes

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