Sodium hydride → HCID 14116940, compound

HRID 1382947Notes

Reaction equation

HRID 1382947 reaction equation
[H-].[Na+].[NH2:3][C:4]1[C:19]([Cl:20])=[CH:18][C:7]([C:8]([NH:10][CH2:11][CH2:12][N:13]([CH2:16][CH3:17])[CH2:14][CH3:15])=[O:9])=[C:6]([OH:21])[CH:5]=1.[CH3:22][O:23][CH2:24][CH2:25][O:26][CH2:27]Cl>CN(C=O)C>[NH2:3][C:4]1[C:19]([Cl:20])=[CH:18][C:7]([C:8]([NH:10][CH2:11][CH2:12][N:13]([CH2:14][CH3:15])[CH2:16][CH3:17])=[O:9])=[C:6]([O:21][CH2:22][O:23][CH2:24][CH2:25][O:26][CH3:27])[CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 775901-(Chloromethoxy)-2-methoxyethaneHCID 9817332o-Desmethyl metoclopramide

Product 1

HCID 14116940HCID 14116940, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a well stirred suspension of sodium hydride (0.34 g of 60%, 0.014 mole) in 5 ml dry DMF was added a solution of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxy benzamide (3.57 g, 0.012 mole) in 15 ml dry DMF at room temperature over 18 minutes. The mixture was then stirred an additional hour giving essentially a clear solution. To this was added dropwise a solution of 2-methoxyethoxymethyl chloride (1.74 g, 0.014 mole) in 5 ml dry DMF. After an additional four hours at ambient temperature, the mixture was concentrated in vacuo, and the residue partitioned between water (200 ml) and methylene chloride (75 ml). The aqueous phase was extracted twice with 75 ml portions of methylene chloride. After combining, the organic phase was washed three times with 50 ml of 10% aqueous sodium hydroxide and three times with brine; dried over sodium sulfate, filtered, concentrated in vacuo, to give 4.26 grams of residue. Crystallization from ether gave 2.53 grams of the title compound, mp 79°-81° C. The NMR spectrum (90 MHz) in CDCl gave the following resonances: δ 8.18 (s, 2H); 6.61 (s, 1H); 5.40 (s, 2H); 4.40 (s, 2H); 3.84 (m, 2H); 3.50 (m, 4H); 3.44 (s, 3H); 2.56 (m, 6H); 1.04 (t, 6H).

Workup

  1. stirringThe mixture was then stirred an additional hour
  2. customgiving essentially a clear solution
  3. concentrationthe mixture was concentrated in vacuo
  4. customthe residue partitioned between water (200 ml) and methylene chloride (75 ml)
  5. extractionThe aqueous phase was extracted twice with 75 ml portions of methylene chloride
  6. washthe organic phase was washed three times with 50 ml of 10% aqueous sodium hydroxide and three times with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cffe26a34fe940a18723c75fd380fe1a
Source dataset
uspto-grants-1989_02
Patent number
US04808624

Reaction notes

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