Sodium hydride → Zetidoline

HRID 596463Notes

Reaction equation

HRID 596463 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:12][CH2:11][NH:10][C:9]2=[O:13])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[CH3:16][C:17]1([CH3:24])[CH2:20][N:19]([CH2:21][CH2:22]Cl)[CH2:18]1>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:12][CH2:11][N:10]([CH2:22][CH2:21][N:19]3[CH2:20][C:17]([CH3:24])([CH3:16])[CH2:18]3)[C:9]2=[O:13])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 841901-(3-Chlorophenyl)-4,5-dihydro-1H-imidazol-2-olHCID 126746081-(2-Chloroethyl)-3,3-dimethylazetidine

Product 1

HCID 72155Zetidoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5 g. of 1-(m-chlorophenyl)-2-imidazolidinone in 30 ml. of dimethylformamide is added at room temperature to a mixture of 1.5 g. of 50% NaH (as a mineral oil emulsion) in 30 ml. of dimethylformamide. The reaction mixture is stirred for an hour at room temperature and 4.5 g. of 3,3-dimethyl-1-(2-chloroethyl)azetidine is added thereto. The mixture is then stirred at room temperature for an additional two hours, then heated for five hours at 80°-85° C. The by-product salts are filtered off and the solvent is removed under vacuum. The residue is taken up with 8 ml. of aqueous 18% HCl and 16 ml. of water and extracted with ether. The water solution is alkalinized by adding aqueous 15% sodium carbonate and extracted with diethyl ether. By evaporation of the organic layer, a residue is obtained that is triturated in light petroleum. Yield 7.24 g., m.p. 84°-85° C. (from hexane). The hydrochloride melts at 191°- 192° C.

Workup

  1. stirringThe mixture is then stirred at room temperature for an additional two hours
  2. temperatureheated for five hours at 80°-85° C
  3. filtrationThe by-product salts are filtered off
  4. customthe solvent is removed under vacuum
  5. extractionof water and extracted with ether
  6. additionby adding aqueous 15% sodium carbonate
  7. extractionextracted with diethyl ether
  8. customBy evaporation of the organic layer
  9. customa residue is obtained
  10. customthat is triturated in light petroleum

Sources & evidence

ORD record
ord-a6362eafb01d4ed28bd57a0e17f25af8
Source dataset
uspto-grants-1977_03
Patent number
US04011238

Reaction notes

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