Hydrochloric Acid → HCID 577954, compound

HRID 395900Notes

Reaction equation

HRID 395900 reaction equation
C[Si](C)(C)Cl.[C:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:8])[CH3:7].Br[CH:16]([CH3:21])[C:17]([O:19][CH3:20])=[O:18].Cl>C(OCC)(=O)C.[Zn]>[OH:8][C:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([CH3:7])[CH:16]([CH3:21])[C:17]([O:19][CH3:20])=[O:18]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 7410AcetophenoneHCID 95576Methyl 2-bromopropionate

Product 1

HCID 577954HCID 577954, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

At room temperature, a three-necked flask fitted with reflux condenser, internal thermometer, dropping funnel and stirrer was charged, under nitrogen protective gas, with 8.6 g of zinc powder (130 mmol) in 53 ml of ethyl acetate. After 2.5 ml of trimethylchlorosilane (19.5 mmol) had been added, the mixture was heated at 65° C. for 30 min, then left to cool to 60° C., following which 10.5 g of acetophenone (87 mmol) were added, and over the course of 6 min, 17.4 g of methyl 2-bromopropionate (104 mmol) were then added dropwise, the temperature being maintained at 65° C. by external cooling. The mixture was stirred at 60° C. for 25 min, and following cooling to 0° C., acidified with 70 ml of 2 N hydrochloric acid to a pH of 1 and stirred for 30 min. Excess zinc was removed by filtration and the organic phase separated. The organic phase was then stirred at 0° C. with 70 ml of 0.5 N hydrochloric acid and finally washed with 30 ml of saturated sodium hydrogen carbonate solution. Following phase separation and drying over sodium sulfate, the solvent was removed by distillation under reduced pressure. Methyl 3-hydroxy-2-methyl-3-phenylbutyrate was obtained in a yield of 15.5 g (91% of theory) with a boiling point of 64° C. (0.03 mbar). The diastereomer ratio of the product was 2:1.

Workup

  1. customAt room temperature, a three-necked flask fitted
  2. temperaturewith reflux condenser
  3. waitleft
  4. temperatureto cool to 60° C.
  5. additionwere added
  6. temperaturethe temperature being maintained at 65° C. by external cooling
  7. temperaturefollowing cooling to 0° C.
  8. stirringstirred for 30 min
  9. customExcess zinc was removed by filtration
  10. customthe organic phase separated
  11. stirringThe organic phase was then stirred at 0° C. with 70 ml of 0.5 N hydrochloric acid
  12. washfinally washed with 30 ml of saturated sodium hydrogen carbonate solution
  13. customFollowing phase separation
  14. dry with materialdrying over sodium sulfate
  15. customthe solvent was removed by distillation under reduced pressure

Sources & evidence

ORD record
ord-ce4227b9ddee47549512cdfe13a773e2
Source dataset
uspto-grants-2003_08
Patent number
US06605716B2

Reaction notes

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