Methanol → Methyl 2-(2,5-dichloro-4-hydroxyphenyl)acetate

Boron tribromide (1.581 mL, 16.72 mmol) was added dropwise to 2-(2,5-dichloro-4-methoxyphenyl)acetic acid (Intermediate 4-4; 655 mg, 2.79 mmol) in dichloromethane (20 mL) at ambient temperature under nitrogen. The resulting solution was stirred at ambient temperature for 60 minutes. The reaction mixture was cautiously added to methanol (100 mL) (—care reaction is vigorous and exothermic—mixture became reasonably warm during the addition) and the mixture was stirred for a further 2 hours at ambient temperature. The reaction mixture was evaporated to dryness and redissolved in DCM (100 mL), and washed sequentially with 2M HCl (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-(2,5-dichloro-4-hydroxyphenyl)acetate (258 mg, 39.4%) as a pale yellow solid.

1. custom—care reaction
2. temperatureexothermic—mixture became reasonably warm during the addition) and the mixture
3. stirringwas stirred for a further 2 hours at ambient temperature
4. customThe reaction mixture was evaporated to dryness
5. dissolutionredissolved in DCM (100 mL)
6. washwashed sequentially with 2M HCl (50 mL) and saturated brine (50 mL)
7. dry with materialThe organic layer was dried over MgSO4
8. filtrationfiltered
9. customevaporated
10. customto afford crude product
11. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane
12. customPure fractions were evaporated to dryness

ORD-Eintrag

ord-24d1f16a6f4843af9a63f07d24a7cfbd

Quelldatensatz

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08188092B2