Reaction #1096

Reaction equation

4-chloro-3-methoxy-2-methylpyridine

phenol

O-benzylhydroxylamine

NaOH

→

4-(O-Benzylhydroxylamino)-3-methoxy-2-methylpyridine

Solvents

CH2Cl2

Conditions

Workup

1. 1
   TemperatureAfter cooling
2. 2
   ExtractionThe aqueous phase is extracted a second time with CH2Cl2
3. 3
   ConcentrationAfter concentrating the combined CH2Cl2 phases, excess O-benzylhydroxylamine
4. 4
   workup.DISTILLATIONis distilled off in vacuo at 0.6 mm
5. 5
   OtherThe residue crystallizes
6. 6
   FiltrationAfter filtering off with suction
7. 7
   Washwashing with hexane 21.6 g=88.4% of product
8. 8
   OtherThe product is recrystallized from ethyl acetate

Procedure

16 g of 4-chloro-3-methoxy-2-methylpyridine, 63 g of phenol and 40 g of O-benzylhydroxylamine are stirred at 120° C. under nitrogen for 4 hours. After cooling, the mixture is shaken with 500 ml of 2N NaOH and CH2Cl2. The aqueous phase is extracted a second time with CH2Cl2. After concentrating the combined CH2Cl2 phases, excess O-benzylhydroxylamine is distilled off in vacuo at 0.6 mm. The residue crystallizes on stirring with hexane. After filtering off with suction and washing with hexane 21.6 g=88.4% of product remain. The product is recrystallized from ethyl acetate. M.p.: 130° C.

Source