Potassium Carbonate → HCID 21291594, compound

HRID 622744Notes

Reaction equation

HRID 622744 reaction equation
[Cl:1]C(OC(Cl)=O)C.[Cl:8][C:9]1[C:29]([C:30]#[N:31])=[CH:28][C:12]([C:13]([NH:15][CH2:16][CH2:17][NH:18][CH2:19][CH2:20]CC2C=CC=CC=2)=[O:14])=[C:11]([O:32][CH3:33])[CH:10]=1.C(=O)([O-])[O-].[K+].[K+]>ClC(Cl)C>[ClH:1].[Cl:8][C:9]1[C:29]([C:30]#[N:31])=[CH:28][C:12]([C:13]([NH:15][CH2:16][CH2:17][NH:18][CH2:19][CH3:20])=[O:14])=[C:11]([O:32][CH3:33])[CH:10]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5213051-Chloroethyl chloroformateHCID 54175326HCID 54175326, compound

Product 1

HCID 21291594HCID 21291594, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

While stirring at 0° C., 2.7 g (19 mmol) of α-chloroethylchloroformate (cf. J. Org. Chem. 49, 2081 (1984)) are added dropwise to a solution of 4.7 g (12.7 mmol) of 4-chloro-5-cyano-N-(2-benzylethylaminoethyl)-2-methoxybenzamide (cf. Example 2) and 90 mg (0.6 mmol) of potassium carbonate in 200 ml of dichloroethane. The whole is then heated under reflux for 3 hours. The reaction mixture is then concentrated to dryness in vacuo, 200 ml of methanol are added to the residue and the whole is heated for 2 hours under reflux. Concentration is repeated, and the residue is taken up in 200 ml of 2N sodium hydroxide solution and extracted three times with chloroform. The combined organic phases are dried over magnesium sulphate, filtered and concentrated by evaporation. The resulting crude material is purified by chromatography over 200 g of silca gel using methylene chloride/methanol/ammonia in a ratio of 100:10:1. The fractions containing the desired product are combined and concentrated by evaporation. The residue is taken up in 50 ml of methanol and, while cooling, the pH is adjusted to 3 using hydrochloric acid. Ether is then added, the hydrochloride crystallising out. 4-chloro-5-cyano-N-(2-ethylaminoethyl)-2-methoxybenzamide hydrochloride having a melting point of 190° -192° C. is obtained.

Workup

  1. temperatureThe whole is then heated
  2. temperatureunder reflux for 3 hours
  3. concentrationThe reaction mixture is then concentrated to dryness in vacuo, 200 ml of methanol
  4. additionare added to the residue
  5. temperaturethe whole is heated for 2 hours
  6. temperatureunder reflux
  7. concentrationConcentration
  8. extractionextracted three times with chloroform
  9. dry with materialThe combined organic phases are dried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated by evaporation
  12. customThe resulting crude material is purified by chromatography over 200 g of silca gel
  13. additionThe fractions containing the desired product
  14. concentrationconcentrated by evaporation
  15. temperaturewhile cooling
  16. additionEther is then added

Sources & evidence

ORD record
ord-7d65a128d66b4cf6879b211fe22a16e1
Source dataset
uspto-grants-1988_09
Patent number
US04772630

Reaction notes

Loading…