Benzyl Alcohol → Ethyl 4-(benzyloxy)-3-oxobutanoate

HRID 2186486Notes

Reaction equation

HRID 2186486 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:10][C:11](=[O:18])[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14].[H-].[Na+]>O1CCCC1>[CH2:1]([O:8][CH2:10][C:11](=[O:18])[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 69484Ethyl 4-chloroacetoacetate

Product 1

HCID 9813448Ethyl 4-(benzyloxy)-3-oxobutanoateYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 112 g (1.04 mol) of benzyl alcohol and 155 g (0.94 mol) of ethyl 4-chloro-3-oxobutyrate was added dropwise to a suspension of 82.9 g (2.07 mol) of 60% sodium hydride in 775 ml of tetrahydrofuran at 35 to 40° C. After the addition, the reaction mixture was stirred at 40° C. for 1 hour. Tetrahydrofuran was recovered from the reaction mixture, and 500 ml of heptane was added to the residue. The resulting solution was added dropwise to 800 ml of water to precipitate crystals, which were separated at room temperature and washed with heptane. To the crystals were added 800 ml of butyl acetate and 1000 ml of 1N hydrochloric acid to conduct extraction. The organic phase was washed successively with 500 ml of a 5% sodium chloride aqueous solution, 500 ml of a 5% sodium hydrogencarbonate aqueous solution, and 500 ml of a 5% sodium chloride aqueous solution to adjust the pH to 6 to 7. Butyl acetate was recovered, and 100 ml of heptane was added to the residue. The mixture was stirred, followed by liquid-liquid separation to obtain 173 g (78%) of ethyl 4-benzyloxy-3-oxobutyrate.

Workup

  1. additionAfter the addition
  2. customTetrahydrofuran was recovered from the reaction mixture, and 500 ml of heptane
  3. additionwas added to the residue
  4. additionThe resulting solution was added dropwise to 800 ml of water
  5. customto precipitate crystals, which
  6. customwere separated at room temperature
  7. washwashed with heptane
  8. additionTo the crystals were added 800 ml of butyl acetate and 1000 ml of 1N hydrochloric acid
  9. extractionextraction
  10. washThe organic phase was washed successively with 500 ml of a 5% sodium chloride aqueous solution, 500 ml of a 5% sodium hydrogencarbonate aqueous solution, and 500 ml of a 5% sodium chloride aqueous solution
  11. customButyl acetate was recovered
  12. addition100 ml of heptane was added to the residue
  13. stirringThe mixture was stirred
  14. customfollowed by liquid-liquid separation

Sources & evidence

ORD record
ord-113b24b55797496285d4b803c0d8e331
Source dataset
uspto-grants-2002_06
Patent number
US06403804B1

Reaction notes

Loading…