Guanidine → Trimethoprim

HRID 1855805Notes

Reaction equation

HRID 1855805 reaction equation
C([C:6]([CH:22](OCC)OCC)([CH2:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[C:13]([O:18][CH3:19])=[C:12]([O:20][CH3:21])[CH:11]=1)[C:7]#[N:8])(OCC)=O.[OH-].[K+].[NH2:31][C:32]([NH2:34])=[NH:33]>C(O)C>[NH2:34][C:32]1[N:33]=[C:7]([NH2:8])[C:6]([CH2:9][C:10]2[CH:15]=[C:14]([O:16][CH3:17])[C:13]([O:18][CH3:19])=[C:12]([O:20][CH3:21])[CH:11]=2)=[CH:22][N:31]=1

Participants

5

Reactant 3

HCID 3520GuanidineHCID 14797Potassium HydroxideHCID 12559126alpha-Carbethoxy-alpha-diethoxymethyl-beta-(3,4,5-trimethoxyphenyl)propionitrile

Product 1

HCID 5578Trimethoprim

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

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.

Workup

  1. temperatureat reflux for one hour
  2. temperaturereflux
  3. customup to 85°
  4. temperatureAfter about 20 hours at reflux the mixture
  5. temperatureto cool
  6. filtrationthe product was filtered
  7. washwashed with ethanol
  8. customThe crude product was purified
  9. additionby treating with hot aqueous acetic acid and reprecipitation with ammonium hydroxide

Sources & evidence

ORD record
ord-b1705b04fe8c4b4395ce925197e29ca6
Source dataset
uspto-grants-1980_08
Patent number
US04216319

Reaction notes

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