Réaction #1942987

Équation de réaction

guanidine

α-carbethoxy-α-diethoxymethyl-β-(3,4,5-trimethoxyphenyl)propionitrile

potassium hydroxide

→

2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine

Solvants

ethanol

ethanol

ethanol

Conditions de réaction

Traitement

1. 1
   Températureat reflux for one hour
2. 2
   Températurereflux
3. 3
   Autreup to 85°
4. 4
   TempératureAfter about 20 hours at reflux the mixture
5. 5
   Températureto cool
6. 6
   Filtrationthe product was filtered
7. 7
   Lavagewashed with ethanol
8. 8
   AutreThe crude product was purified
9. 9
   workup.ADDITIONby treating with hot aqueous acetic acid and reprecipitation with ammonium hydroxide

Mode opératoire

A solution of α-carbethoxy-α-diethoxymethyl-β-(3,4,5-trimethoxyphenyl)propionitrile (7.9 g, 0.02 mol) and an equivalent amount of potassium hydroxide in ethanol (50 ml) was heated at reflux for one hour. A solution of guanidine (0.07 mol) in ethanol (50 ml) was added, and reflux was resumed. Some ethanol was allowed to boil off bringing the reaction temperature up to 85°. After about 20 hours at reflux the mixture was allowed to cool, and the product was filtered and washed with ethanol. The crude product was purified by treating with hot aqueous acetic acid and reprecipitation with ammonium hydroxide. The yield of purified trimethoprim (m.p. 197°-198°) was 3.6 g (62%), its identity being confirmed by an NMR spectrum.

Source