2-Aminophenol → N-(2-Hydroxyphenyl)-3-methoxy-4-methylbenzamide

3-Methoxy-4-methyl benzoic acid (1.2 g, 7.2 mmol) and thionyl chloride (10 mL) was heated to reflux conditions under argon until no starting material was observed by TLC. After cooling mixture to rt and concentration in vacuo, the resulting brown oil was dissolved in THF (15 mL) and slowly added to a cooled mixture of 2-aminophenol (780 mg, 7.1 mmol), diisopropylethyl amine (1.5 mL, 8.6 mmol) and THF (20 mL) at 0° C. Reaction mixture was allowed to warm to rt. After one hour, no starting material acid was observed by TLC. After concentrating reaction mixture in vacuo, the resulting brown oil was purified by flash chromatography on silica gel, using 1:4 EtOAc:hexanes. This afforded the desired intermediate, N-(2-hydroxyphenyl)-3-methoxy-4-methylbenzamide, as a yellow solid. A mixture of N-(2-hydroxyphenyl)-3-methoxy-4-methylbenzamide (1.5 g, 5.88 mmol), toluene (30 mL), p-toluenesulfonic acid monohydrate (7.6 g, 40 mmol) and molecular sieves was refluxed overnight. After cooling reaction to rt, filtered washing with warn chloroform and concentrated filtrate in vacuo. The resulting brown oil was purified by flash chromatography on silica gel using 1:4 EtOAc:hexanes to give the desired intermediate, 2-(3-methoxy-4-methylphenyl)-1,3-benzoxazole, as a colorless solid.

1. temperatureto reflux conditions under argon until no starting material
2. concentrationconcentration in vacuo
3. dissolutionthe resulting brown oil was dissolved in THF (15 mL)
4. customReaction mixture
5. temperatureto warm to rt
6. concentrationAfter concentrating
7. customreaction mixture in vacuo
8. customthe resulting brown oil was purified by flash chromatography on silica gel

ORD-Eintrag

ord-86e2c3eed48a4101adc2ec27674f9f15

Quelldatensatz

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07087601B2