2-Methoxybenzaldehyde → 5-(2-Methoxyphenyl)-1,3-oxazole

HRID 1272192Notes

Reaction equation

HRID 1272192 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH:5]=[O:6].S([CH2:21][N+:22]#[C-:23])(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CO>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[C:5]1[O:6][CH:23]=[N:22][CH:21]=1

Participants

5

Reactant 3

HCID 86582-MethoxybenzaldehydeHCID 11430Potassium CarbonateHCID 161915Tosylmethyl isocyanide

Product 1

HCID 167406765-(2-Methoxyphenyl)-1,3-oxazoleYield 70.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 2-methoxybenzaldehyde (10.0 g, 73.4 mmol), tosylmethylisocyanide (14.34 g, 73.4 mmol) and potassium carbonate (10.14 g, 73.4 mmol) in 220 ml methanol is heated at reflux for 6 hours. The solvent is removed under reduced pressure and the residue poured into ice-water (800 ml). The precipitate is collected by filtration, washed with water, and dried in vacuo to give 9.05 g of 5-(2-methoxyphenyl)oxazole (70%). Boron tribromide (1M in dichloromethane, 36 ml) is added slowly to a cold solution (0° C.) of the above oxazole (3.0 g, 17.1 mmol) in dichloromethane (215 ml). After stirring overnight at room temperature, ice-water (50 ml) is added carefully. The aqueous layer is extracted with dichloromethane (50 ml), and the combined organic layers are dried over sodium sulfate and concentrated under reduced pressure. The precipitate which formed after addition of dichloromethane (70 ml) is collected by filtration, heated with dichloromethane (15 ml), and filtered again to give 3.16 g of 2-(5-oxazolyl)phenol. This phenolic product is reacted with (2S)-glycidyl 3-nitrobenzenesulfonate substantially as described for Epoxide 1 to give 400 mg of the title epoxide (9.5%).

Workup

  1. temperatureis heated
  2. temperatureat reflux for 6 hours
  3. customThe solvent is removed under reduced pressure
  4. additionthe residue poured into ice-water (800 ml)
  5. filtrationThe precipitate is collected by filtration
  6. washwashed with water
  7. customdried in vacuo

Sources & evidence

ORD record
ord-e4fd0d91a42f48d8b8618ea29592a4d1
Source dataset
uspto-grants-2007_04
Patent number
US07208505B2

Reaction notes

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