Sodium hydride → 2-(3-(Benzyloxy)-4-bromo-5-methoxyphenyl)-5-methyloxazole

HRID 579306Notes

Reaction equation

HRID 579306 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:18]=[C:19]([O:22][CH3:23])[C:20]=1[Br:21])[C:12]([NH:14][CH2:15][C:16]#[CH:17])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+]>O1CCOCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:12]2[O:13][C:16]([CH3:17])=[CH:15][N:14]=2)[CH:18]=[C:19]([O:22][CH3:23])[C:20]=1[Br:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 867106063-(benzyloxy)-4-bromo-5-methoxy-N-(prop-2-yn-1-yl)benzamide

Product 1

HCID 867106072-(3-(Benzyloxy)-4-bromo-5-methoxyphenyl)-5-methyloxazoleYield 43.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-(benzyloxy)-4-bromo-5-methoxy-N-(prop-2-yn-1-yl)benzamide (0.455 g, 1.22 mmol) in dioxane (12 mL) was added sodium hydride (60% wt, 0.146 g, 3.65 mmol) and the mixture was heated at reflux for six hours. The mixture was cooled to room temperature, quenched by slow addition of water, and diluted with ethyl acetate. The mixture was washed with water, saturated sodium bicarbonate, brine, then dried over magnesium sulfate and concentrated. Flash column chromatography (12 g silica, 2% ethyl acetate in DCM) provided 2-(3-(benzyloxy)-4-bromo-5-methoxyphenyl)-5-methyloxazole (198 mg) as an off-white solid. MS=374 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.55 (d, J=7.58 Hz, 2H), 7.43 (t, J=7.33 Hz, 2H), 7.32-7.39 (m, 2H), 7.27 (d, J=2.02 Hz, 1H), 6.89 (d, J=1.01 Hz, 1H), 5.27 (s, 2H), 4.02 (s, 3H), 2.44 (d, J=1.52 Hz, 3H).

Workup

  1. temperature0.146 g, 3.65 mmol) and the mixture was heated
  2. temperatureat reflux for six hours
  3. customquenched by slow addition of water
  4. additiondiluted with ethyl acetate
  5. washThe mixture was washed with water, saturated sodium bicarbonate, brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-a698b724332b463eb918082a0c1a772d
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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