Acetic Acid → HCID 13808681, compound

HRID 648706Notes

Reaction equation

HRID 648706 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]([O:13]C)=O)=[C:5]([O:15][CH3:16])[C:4]=1OC=C=O.[H-].[Na+].[C:23]([OH:27])(C)(C)C.[C:28](O)(=[O:30])C>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]2[CH2:9][CH2:10][C:11](=[O:13])[CH:16]([C:28]([O:27][CH3:23])=[O:30])[O:15][C:5]=2[CH:4]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6386tert-ButanolHCID 24758Sodium hydrideHCID 86742083HCID 86742083, compound

Product 1

HCID 13808681HCID 13808681, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of 15 g of methyl 3-(4-methoxy-2-methoxy-carbonylmethyloxyphenyl)propionate in 200 ml of toluene is added dropwise to a suspension of 5.6 g of 60% oily sodium hydride in 200 ml of toluene to which 0.4 ml of tert-butanol is added, for a period of 8 hours with heating under refluxing. The reaction mixture is heated under refluxing for 30 minutes and allowed to stand overnight, and then poured into ice water containing 10 ml of acetic acid. The organic layer is separated, washed with water, dried and evaporated under reduced pressure. The residue is purified by column chromatography on silica gel (eluant: hexane:ethyl acetate=4:1) to give 9.5 g of methyl 8-methoxy-3-oxo-2,3,4,5-tetrahydro-1-benzoxepin-2-carboxylate as a colorless oil. A mixture of 7.4 g of methyl 8-methoxy-3-oxo-2,3,4,5-tetrahydro-1-benzoxepin-2-carboxylate, 10.9 g of 1-bromo-3-chloropropane, 1.5 g of potassium iodide, 10 g of anhydrous potassium carbonate and 300 ml of acetonitrile is heated under refluxing with stirring for 5 hours. After cooling, the inorganic substances are filtered off and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (eluant: hexane:ethyl acetate=8:1) to give 9 g of methyl 2-(3-chloropropyl)-8-methoxy-3-oxo-2,3,4,5-tetrahydro-1-benzoxepin-2-carboxylate as an oil. In 100 ml of methanol is dissolved 9 g of methyl 2-(3-chloropropyl)-8-methoxy-3-oxo-2,3,4,5-tetrahydro-1-benzoxepin-2-carboxylate, and 0.6 g of sodium borohydride is added in small portions to the solution under ice-cooling with stirring. The reaction mixture is concentrated under reduced pressure, and the residue is treated with water and extracted with ethyl acetate. The organic layer is washed with water, dried and evaporated under reduced pressure, and the residue is purified by column chromatography on silica gel (eluant: hexane:ethyl acetate=3:1) to give 3.3 g of methyl trans-2-(3-chloropropyl)-3-hydroxy-8-methoxy-2,3,4,5-tetrahydro-1-benzoxepin-2-carboxylate as a colorless oil from the first fraction eluted.

Workup

  1. additionis added, for a period of 8 hours
  2. temperaturewith heating
  3. temperatureunder refluxing
  4. temperatureThe reaction mixture is heated
  5. temperatureunder refluxing for 30 minutes
  6. customThe organic layer is separated
  7. washwashed with water
  8. customdried
  9. customevaporated under reduced pressure
  10. customThe residue is purified by column chromatography on silica gel (eluant: hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-72be7171664d4fbda0b0ec8c9e1af8b4
Source dataset
uspto-grants-1988_04
Patent number
US04736031

Reaction notes

Loading…