Benzaldehyde → tert-Butyl 3-hydroxy-3-phenylpropanoate

HRID 394908Notes

Reaction equation

HRID 394908 reaction equation
C[Si](C)(C)Cl.Br[CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[CH:15](=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Cl>C(OCC)(=O)C.[Zn]>[OH:22][CH:15]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9]

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 79177tert-Butyl bromoacetate

Product 1

HCID 219282tert-Butyl 3-hydroxy-3-phenylpropanoate

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

At room temperature, a three-neck flask equipped with a reflux condenser, internal thermometer, dropping funnel and stirrer under nitrogen protective gas was initially charged with 8 g of zinc powder (122 mmol) in 47 ml of ethyl acetate. After 1.9 ml of trimethylchlorosilane (15 mmol) had been added, the mixture was heated to 60° C. for 15 min, then allowed to cool to 55° C. and 22 g of undiluted tert-butyl bromoacetate (113 mmol) were subsequently added dropwise within 5 min, and the temperature was maintained at 65° C. by external cooling. The mixture was then stirred at 50° C. for 10 min. After cooling to 0° C., 10 g of undiluted benzaldehyde (94 mmol) were added, and the temperature was maintained at 10° C. by external cooling. After stirring had been continued at 25° C. for 90 min and 35° C. for 15 min, 40 ml of ethyl acetate were added, the mixture was cooled to 15° C., acidified with 17 ml of 20% hydrochloric acid to a pH of 1-2 and the mixture was stirred for 10 min, during which excess zinc dissolved. The organic phase was then removed. The organic phase was then stirred with 15 ml of concentrated ammonia solution at 25° C. for 10 min. After the phase separation, drying was effected over sodium sulfate and the solvent was distilled off under reduced pressure. Tert-butyl 3-hydroxy-3-phenylpropionate was obtained in a yield of 20.3 g (97% of theory) and had a boiling point of 102° C. (1.5 mbar).

Workup

  1. customAt room temperature, a three-neck flask equipped with a reflux condenser
  2. temperatureto cool to 55° C.
  3. temperaturethe temperature was maintained at 65° C. by external cooling
  4. temperatureAfter cooling to 0° C.
  5. temperaturethe temperature was maintained at 10° C. by external cooling
  6. stirringAfter stirring
  7. waithad been continued at 25° C. for 90 min and 35° C. for 15 min
  8. temperaturethe mixture was cooled to 15° C.
  9. dissolutiondissolved
  10. customThe organic phase was then removed
  11. stirringThe organic phase was then stirred with 15 ml of concentrated ammonia solution at 25° C. for 10 min
  12. customAfter the phase separation
  13. customdrying
  14. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-4179534b9ad44ffda1aebbb09a8f7174
Source dataset
uspto-grants-2003_08
Patent number
US06603034B2

Reaction notes

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