Water → HCID 11673685, compound

HRID 853172Notes

Reaction equation

HRID 853172 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][CH:8]=1.[H-].[Na+].Cl[CH2:21][C:22]([NH2:24])=[O:23].O>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][O:14][CH2:21][C:22]([NH2:24])=[O:23])=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6580ChloroacetamideHCID 24758Sodium hydrideHCID 887902Safinamide Impurity 8

Product 1

HCID 11673685HCID 11673685, compoundYield 5.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 500 mg of [4-(3-fluoro-benzyloxy)-phenyl]-methanol [Example 25b)] in 10 ml of tetrahydrofurane was treated at room temperature with 57 mg of sodium hydride (55% dispersion in oil) and stirred for 1 h. Thereafter, 183 mg of chloroacetamide were added and the mixture was heated to reflux for 48 h. For the working-up, the cooled mixture was treated with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulphate and evaporated under reduced pressure. For purification, the crude material obtained was chromatographed on silica gel using a gradient of dichloromethane to a 4:1-mixture-mixture of dichloromethane and methanol as the eluent. After crystallisation from ether, there were obtained 29 mg (5% of theory) of 2-[4-(3-fluoro-benzyloxy)-benzyloxy]-acetamide as a white solid; MS: m/e=307 (M+NH4)+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 48 h
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over magnesium sulphate
  5. customevaporated under reduced pressure
  6. customFor purification
  7. customthe crude material obtained
  8. customwas chromatographed on silica gel using a gradient of dichloromethane to a 4
  9. addition1-mixture-mixture of dichloromethane and methanol as the eluent
  10. customAfter crystallisation from ether

Sources & evidence

ORD record
ord-5211eaa6135b46b0b978df97490775d3
Source dataset
uspto-grants-2007_08
Patent number
US07253318B2

Reaction notes

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