Ethylenediamine → 3-(Phenylmethoxy)benzenepropanol

HRID 2084373Notes

Reaction equation

HRID 2084373 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=1)[CH:12]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:17](OCCP(OCC)(OCC)=O)(=[O:19])[CH3:18].[H-].[Na+].C(N)CN.[H][H]>CN(C=O)C.C(O)C.[C].[Pd]>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH2:12][CH2:18][CH2:17][OH:19])[CH:14]=[CH:15][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 3301EthylenediamineHCID 24758Sodium hydrideHCID 743423-BenzyloxybenzaldehydeHCID 124696282-(Diethoxyphosphoryl)ethyl acetateHCID 178418361HCID 178418361, compound

Product 1

HCID 126481553-(Phenylmethoxy)benzenepropanolYield 59.2%

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

In an argon stream, 3-benzyloxybenzaldehyde (21.3 g) and diethylphosphonoethyl acetate (23.6 g) were suspended in dry DMF (250 ml). Under ice cooling and stirring, 65% oily sodium hydride (3.88 g) was added little by little; after completion of this addition, the mixture was stirred at room temperature for 2 hours. After the solvent was distilled off, the residue was dissolved in ethyl acetate and washed with water and saturated saline, after which it was dried over anhydrous sodium sulfate. Under reduced pressure, the solvent was distilled off to yield 33.15 g of a crude product of ethyl (E)-3-[3-(benzyloxy)phenyl]-2-propenate as an oily substance. This product was dissolved in ethanol (406 ml); ethylenediamine-treated 5% palladium carbon [Pd—C (en), 2.7 g] was added, followed by vigorous stirring in a hydrogen atmosphere. Hydrogen (1.75 L) was consumed to complete hydrogenation, and the catalyst was filtered off. Under reduced pressure, the solvent was distilled off; the residue was dissolved in dehydrated THF (120 ml). This solution was added drop by drop to a mixture of lithium aluminum hydride (4.61 g) suspended in dehydrated THF (120 ml) under ice cooling. The reaction mixture was stirred under ice cooling for 1.5 hours and at room temperature for 1 hour. The reaction mixture was added to ice water and acidified, after which it was extracted with ethyl acetate, washed with water and saturated saline, after which it was dried over anhydrous sodium sulfate. Under reduced pressure, the solvent was distilled off; the residue was purified by silica gel column chromatography to yield the titled compound (14.39 g) as a colorless oily substance.

Workup

  1. additionafter completion of this addition
  2. stirringthe mixture was stirred at room temperature for 2 hours
  3. distillationAfter the solvent was distilled off
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washwashed with water and saturated saline
  6. dry with materialafter which it was dried over anhydrous sodium sulfate
  7. distillationUnder reduced pressure, the solvent was distilled off
  8. customto yield 33.15 g of a crude product of ethyl (E)-3-[3-(benzyloxy)phenyl]-2-propenate as an oily substance
  9. additionwas added
  10. customHydrogen (1.75 L) was consumed
  11. filtrationthe catalyst was filtered off
  12. distillationUnder reduced pressure, the solvent was distilled off
  13. dissolutionthe residue was dissolved in dehydrated THF (120 ml)
  14. additionThis solution was added drop by drop
  15. additionto a mixture of lithium aluminum hydride (4.61 g)
  16. stirringThe reaction mixture was stirred under ice cooling for 1.5 hours and at room temperature for 1 hour
  17. additionThe reaction mixture was added to ice water
  18. extractionafter which it was extracted with ethyl acetate
  19. washwashed with water and saturated saline
  20. dry with materialafter which it was dried over anhydrous sodium sulfate
  21. distillationUnder reduced pressure, the solvent was distilled off
  22. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d06511c0a01b47e0a576208dac73938a
Source dataset
uspto-grants-2004_04
Patent number
US06716863B2

Reaction notes

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