1,3-Dibromopropane → Benzyl [2-(3-bromopropoxy)phenyl]acetate

HRID 1721218Notes

Reaction equation

HRID 1721218 reaction equation
C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].[Br:25][CH2:26][CH2:27][CH2:28]Br>C(#N)C>[Br:25][CH2:26][CH2:27][CH2:28][O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16]

Participants

5

Reactant 3

HCID 80011,3-DibromopropaneHCID 11430Potassium CarbonateHCID 15525522HCID 15525522, compound

Product 1

HCID 22417251Benzyl [2-(3-bromopropoxy)phenyl]acetate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 100 g of 2-hydroxyphenylacetic acid, 75 cm3 of benzyl alcohol and 0.5 g of paratoluenesulphonic acid in 1400 cm3 of toluene is refluxed for 2 hours while removing the water formed. After cooling, treating with 3 g of animal black and filtering, the reaction mixture is concentrated to 150 cm3 and supplemented with 300 cm3 of isopropyl oxide. The crystals obtained by cooling to 0° C. are drained, washed and dried to give 82.5 g of benzyl 2-hydroxyphenylacetate. 174 g of potassium carbonate are added to a solution of 153 g of this ester in a mixture of 500 cm3 of 1,3-dibromopropane and 2500 cm3 of acetonitrile and the mixture is refluxed for 17 hours. The reaction mixture is cooled, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is taken up in 500 cm3 of ethyl acetate and the organic phase is washed twice with 400 cm3 of water and twice with 250 cm3 of a saturated solution of sodium chloride and then dried and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.2-0.063 mm, diameter 9 cm, height 55 cm), eluting with a cyclohexane and ethyl acetate mixture (95/5 by volume) and collecting fractions of 500 cm3. Fractions 12 to 18 are pooled and concentrated to dryness under reduced pressure (2.7 kPa) to give 90 g of benzyl 2-(3-bromopropoxy)phenylacetate in the form of a yellow oil. A solution of 40 g of this product in 500 cm3 of acetonitrile is heated in an autoclave with 27 g of sodium iodide and 90 g of dimethylamine for 16 hours at 80° C. The reaction mixture is cooled, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is purified by acid-base treatment to give 29.3 g of benzyl 2-(3-dimethylaminopropoxy)phenylacetate in the form of a yellow oil. Hydrogenation of this ester at atmospheric pressure at 40° C. in ethyl acetate in the presence of palladium hydroxide, followed by crystallization from ethyl acetate, lead to 17.5 g of 2-(3-dimethylaminopropoxy)phenylacetic acid in the form of white crystals; melting point 98° C.

Workup

  1. temperaturethe mixture is refluxed for 17 hours
  2. temperatureThe reaction mixture is cooled
  3. filtrationfiltered
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. washthe organic phase is washed twice with 400 cm3 of water and twice with 250 cm3 of a saturated solution of sodium chloride
  6. customdried
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe residue is chromatographed on a silica gel column (particle size 0.2-0.063 mm, diameter 9 cm, height 55 cm)
  9. washeluting with a cyclohexane and ethyl acetate mixture (95/5 by volume)
  10. customcollecting fractions of 500 cm3
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-e1506d4e5eee4011bd36b7c852effdfb
Source dataset
uspto-grants-1996_04
Patent number
US05508433

Reaction notes

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