Sodium hydride → 2-(3-(Benzyloxy)-4-bromo-5-((2-(trimethylsilyl)ethoxy)methoxy)phenyl)-5-methyloxazole

HRID 1027245Notes

Reaction equation

HRID 1027245 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:12]=[C:13]([CH:20]=[C:21]([O:24][CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:22]=1[Br:23])[C:14]([NH:16][CH2:17][C:18]#[CH:19])=[O:15])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>O1CCOCC1>[CH2:3]([O:10][C:11]1[CH:12]=[C:13]([C:14]2[O:15][C:18]([CH3:19])=[CH:17][N:16]=2)[CH:20]=[C:21]([O:24][CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:30])([CH3:32])[CH3:31])[C:22]=1[Br:23])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 867106513-(benzyloxy)-4-bromo-N-(prop-2-ynyl)-5-((2-(trimethylsilyl)ethoxy)-methoxy)benzamide

Product 1

HCID 867106522-(3-(Benzyloxy)-4-bromo-5-((2-(trimethylsilyl)ethoxy)methoxy)phenyl)-5-methyloxazoleYield 51.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Sodium hydride (0.953 g, 39.7 mmol) was added to a solution of 3-(benzyloxy)-4-bromo-N-(prop-2-ynyl)-5-((2-(trimethylsilyl)ethoxy)-methoxy)benzamide (6.49 g, 13.2 mmol) in dioxane (100 mL) and the mixture was heated at reflux overnight. The solution was cooled to room temperature and quenched by slow addition of saturated NaHCO3. The solution was diluted with ethyl acetate/diethyl ether and washed with water (5×), saturated NaHCO3, brine, dried over sodium sulfate and concentrated to a thick brown liquid. Flash chromatography (80 g silica gel, 5-40% EtOAc in heptane) provided 2-(3-(benzyloxy)-4-bromo-5-((2-(trimethylsilyl)ethoxy)methoxy)phenyl)-5-methyloxazole as an orange oil (3.33 g). MS (M+1)=492.21. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.30-7.58 (m, 7H), 6.86 (d, J=1.0 Hz, 1H), 5.40 (s, 2H), 5.25 (s, 2H), 3.80-3.92 (m, 2H), 2.41 (s, 3H), 0.95-1.04 (m, 2H), 0.02 (s, 10H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux overnight
  3. customquenched by slow addition of saturated NaHCO3
  4. additionThe solution was diluted with ethyl acetate/diethyl ether
  5. washwashed with water (5×), saturated NaHCO3, brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to a thick brown liquid

Sources & evidence

ORD record
ord-da5f05a1372f4e91a211fc73f72ea7a8
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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