Chloromethyl Methyl Ether → 3-(4-Benzyloxy-2-methoxymethoxyphenyl)propionamide

HRID 733341Notes

Reaction equation

HRID 733341 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]([NH2:21])=[O:20])=[C:13]([OH:22])[CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:23][O:24][CH2:25]Cl>CN(C)C=O>[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]([NH2:21])=[O:20])=[C:13]([O:22][CH2:23][O:24][CH3:25])[CH:12]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 178562633-(4-Benzyloxy-2-hydroxyphenyl)propionamide

Product 1

HCID 178562353-(4-Benzyloxy-2-methoxymethoxyphenyl)propionamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred suspension of 5.64 g of 60% sodium hydride in oil in 628 mL of N,N-dimethylformamide was added 34.8 g of 3-(4-benzyloxy-2-hydroxyphenyl)propionamide under ice-cooling, and the mixture was stirred at 50° C. for 40 minutes. To the reaction mixture was added 12.39 g of chloromethyl methyl ether under ice-cooling, and the mixture was stirred at room temperature for 15 hours. After the reaction mixture was concentrated under reduced pressure to remove the solvent, the residue was poured into a mixture of 500 mL of ethyl acetate, 100 mL of toluene, and 200 mL of water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give a colorless solid. The solid was triturated in ethyl acetate-diisopropyl ether to collect by filtration of 35.3 g of 3-(4-benzyloxy-2-methoxymethoxy-phenyl)propionamide as a colorless solid.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred at room temperature for 15 hours
  4. concentrationAfter the reaction mixture was concentrated under reduced pressure
  5. customto remove the solvent
  6. additionthe residue was poured into a mixture of 500 mL of ethyl acetate, 100 mL of toluene, and 200 mL of water
  7. customThe organic layer was separated
  8. washwashed with water
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated under reduced pressure
  12. customto give a colorless solid
  13. customThe solid was triturated in ethyl acetate-diisopropyl ether
  14. filtrationto collect by filtration of 35.3 g of 3-(4-benzyloxy-2-methoxymethoxy-phenyl)propionamide as a colorless solid

Sources & evidence

ORD record
ord-19d2f38f56fa47a08da8ec298be988f2
Source dataset
uspto-grants-2009_09
Patent number
US07589126B2

Reaction notes

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