Metoclopramide → o-Desmethyl metoclopramide

HRID 1382944Notes

Reaction equation

HRID 1382944 reaction equation
[NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])=[O:7])=[C:4]([O:19]C)[CH:3]=1.[OH-].[Na+]>C(O)C(O)C>[NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:12][CH3:13])[CH2:14][CH3:15])=[O:7])=[C:4]([OH:19])[CH:3]=1

Participants

4

Reactant 2

HCID 4168MetoclopramideHCID 14798Sodium Hydroxide

Product 1

HCID 9817332o-Desmethyl metoclopramideYield 32.5%

Reagents, catalysts & solvents 1

HCID 1030Propylene GlycolSolvent

Procedure

A mixture of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide (29.5 g, 0.1 mole), sodium hydroxide pellets (4.0 g, 0.1 mole) and 1,2-propanediol (70 ml) was stirred and heated under reflux for 20 hours followed by concentration in vacuo. The residue was treated with 1N HCl (100 ml) and again concentrated in vacuo. The residue was chromatographed on silica using methylene chloride (90), methanol (10), ammonia (0.5) solvent system. The appropriate fractions were combined and concentrated in vacuo and the residue crystallized from ether to give 9.3 g of product. This was dissolved in hot water, and the solution filtered over charcoal. The filtrate was cooled and filtered to give 6.7 g of tan colored title compound, mp 126°-7° (U.S. Pat. No. 3,357,978 reports mp 160° ).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 20 hours
  3. concentrationfollowed by concentration in vacuo
  4. additionThe residue was treated with 1N HCl (100 ml)
  5. concentrationagain concentrated in vacuo
  6. customThe residue was chromatographed on silica
  7. concentrationconcentrated in vacuo
  8. customthe residue crystallized from ether

Sources & evidence

ORD record
ord-ee4c00dfb7dc4c85b8ff4dcc2157f37b
Source dataset
uspto-grants-1989_02
Patent number
US04808624

Reaction notes

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