Metoclopramide → 4-amino-5-chloro-N-(2-(diethylamino)ethyl)-2-hydroxybenzamide hydrochloride

HRID 1382942Notes

Reaction equation

HRID 1382942 reaction equation
[H-].[Na+].C(S)C.[H][H].[NH2:8][C:9]1[C:24]([Cl:25])=[CH:23][C:12]([C:13]([NH:15][CH2:16][CH2:17][N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[O:14])=[C:11]([O:26]C)[CH:10]=1>CN(C=O)C>[ClH:25].[NH2:8][C:9]1[C:24]([Cl:25])=[CH:23][C:12]([C:13]([NH:15][CH2:16][CH2:17][N:18]([CH2:19][CH3:20])[CH2:21][CH3:22])=[O:14])=[C:11]([OH:26])[CH:10]=1

Participants

6

Reactant 4

HCID 4168MetoclopramideHCID 6343EthanethiolHCID 24758Sodium hydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 141168774-amino-5-chloro-N-(2-(diethylamino)ethyl)-2-hydroxybenzamide hydrochlorideYield 196.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a cooled (<10°) stirred suspension of sodium hydride (57.44 g of 60%, 1.436 moles) in DMF (1275 ml) was added dropwise a cold solution of ethanethiol (89.22 g, 1.436 moles) in DMF (250 ml). After hydrogen evolution had ceased 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide (287.0 g, 0.957 moles) (prepared according to U.S. Pat. No. 3,357,978 [1965]) was added and the mixture was heated in an oil bath at 100°-105° for 90 minutes. The solvent was removed in vacuo and the residue partitioned between methylene chloride (800 ml) and water (400 ml). The aqueous layer was washed with another portion of methylene chloride and the combined organic extracts were backwashed with water (150 ml). The combined aqueous phase was cooled in an ice bath and treated with concentrated hydrochloric acid (200 ml). After 20 minutes the precipitate was collected by filtration, sucked briefly on the filter, slurried with methanol (500 ml) and again filtered. The product was dried in vacuo to give 302.3 g (98%) of the title compound as a light beige solid, mp 235°-237°.

Workup

  1. temperatureTo a cooled (<10°)
  2. customprepared
  3. temperaturethe mixture was heated in an oil bath at 100°-105° for 90 minutes
  4. customThe solvent was removed in vacuo
  5. customthe residue partitioned between methylene chloride (800 ml) and water (400 ml)
  6. washThe aqueous layer was washed with another portion of methylene chloride
  7. temperatureThe combined aqueous phase was cooled in an ice bath
  8. additiontreated with concentrated hydrochloric acid (200 ml)
  9. filtrationAfter 20 minutes the precipitate was collected by filtration
  10. filtrationagain filtered
  11. customThe product was dried in vacuo

Sources & evidence

ORD record
ord-53a0745f86304bc190719b2865881d38
Source dataset
uspto-grants-1989_02
Patent number
US04808624

Reaction notes

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