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

HRID 1027210Notes

Reaction equation

HRID 1027210 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 heated at reflux for six hours. The mixture was cooled to RT, quenched by slow addition of water and diluted with ethyl acetate. The mixture was washed with water, saturated sodium bicarbonate, brine, 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 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-3eac5a320f6a44c28bc1e09ea500d50c
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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