Benzyl Alcohol → 4-benzyloxy-7-methoxy-8-methylquinoline N-oxide

HRID 402151Notes

Reaction equation

HRID 402151 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:12]1[C:21]2[C:16](=[C:17]([CH3:24])[C:18]([O:22][CH3:23])=[CH:19][CH:20]=2)[N+:15]([O-:25])=[CH:14][CH:13]=1.O>CN(C=O)C>[CH2:3]([O:10][C:12]1[C:21]2[C:16](=[C:17]([CH3:24])[C:18]([O:22][CH3:23])=[CH:19][CH:20]=2)[N+:15]([O-:25])=[CH:14][CH:13]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 962WaterHCID 24758Sodium hydrideHCID 576079424-Chloro-7-methoxy-8-methylquinoline N-oxide

Product 1

HCID 576079514-benzyloxy-7-methoxy-8-methylquinoline N-oxideYield 59.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (973 mg, 60% in mineral oil, 24.3 mmol) was added at 0° C., under inert atmosphere, to benzylalcohol (2.96 mL, 28.6 mmol) in DMF (10 mL). After 5 min at 0° C., the solution was warmed up to room temperature. After 10 min at room temperature, 4-chloro-7-methoxy-8-methylquinoline N-oxide (61, 3.2 g, 14.3 mmol) was added in one potion. The resulting black solution was stirred at room temperature under inert atmosphere for another 30 min, then poured into ice-cooled water, and extracted 4 times with AcOEt. Combined organic layers were dried (Na2SO4) and evaporated. The residue was purified by column chromatography (gradient AcOEt/CH2Cl2, 1:1 to 1:0, then AcOEt/MeOH 9:1) to give 2.5 g (59%) of the target product 62 as a yellow powder: m/z=296 (M+H)+.

Workup

  1. waitAfter 10 min at room temperature
  2. additionpoured into ice-
  3. extractionextracted 4 times with AcOEt
  4. dry with materialCombined organic layers were dried (Na2SO4)
  5. customevaporated
  6. customThe residue was purified by column chromatography (gradient AcOEt/CH2Cl2, 1:1 to 1:0

Sources & evidence

ORD record
ord-cf0beee303bc4975872d337d2e5d3987
Source dataset
uspto-grants-2014_06
Patent number
US08741926B2

Reaction notes

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