Ethyl Bromide → Ethyl 2-hydroxy-2-methyl-4-phenylbut-3-ynoate

HRID 246801Notes

Reaction equation

HRID 246801 reaction equation
C(Br)C.[Mg].[C:5]1([C:11]#[CH:12])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[C:13]([O:18][CH2:19][CH3:20])(=[O:17])[C:14]([CH3:16])=[O:15].[Cl-].[NH4+]>CCOCC>[CH2:19]([O:18][C:13](=[O:17])[C:14]([OH:15])([CH3:16])[C:12]#[C:11][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH3:20]

Participants

7

Reactant 5

HCID 6332Ethyl BromideHCID 10821PhenylacetyleneHCID 12041Ethyl pyruvateHCID 25517Ammonium ChlorideHCID 5462224Magnesium

Product 1

HCID 13278090Ethyl 2-hydroxy-2-methyl-4-phenylbut-3-ynoateYield 41%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent4×

Conditions

Temperature
25 °C

Procedure

A Grignard reagent was prepared under dry nitrogen by the addition over a 1 hour period of a solution comprising 10.9 g (0.10 mole) of ethyl bromide in 15 ml of anhydrous ether to a magnetically stirred suspension of 2.4 g (0.10 g atom) of clean magnesium metal turnings in 70 ml of dry ether. Stirring at 25° C. was continued for an additional hour and then a solution of 10.2 g (0.10 mole) of phenyl acetylene in 15 ml of dry ether was added over 30 minutes. The stirred solution was then heated at reflux for one hour, during which time the acetylenic Grignard reagent separated into a two phase grey-black liquid. After cooling, the two phase liquid was transferred under dry nitrogen to a 200 ml addition funnel followed by flushing with two 15 ml portions of dry ether. The contents of the funnel were rendered homogeneous, by efficient overhead mechanical stirring, and this mixture was added over 35 minutes to a magnetically stirred solution of 11.6 g (0.10 mole) of ethyl pyruvate in 80 ml of dry ether cooled to -20° C. The mixture was stirred at -20° C. for 2 hours and allowed to warm to room temperature overnight. The resulting yellow-orange solution was cautiously treated with 75 ml of saturated ammonium chloride solution and after stirring for 5 minutes, the phases were separated. The aqueous phase was extraced with two 60 ml portions of ether and the combined organic phases were washed with three 75 ml portions of brine and dried over MgSO4. After filtration and concentration at the stripper, a residual reddish-orange oil (19.6 g) was fractionated through a 15 cm Vigreux column to afford, after a small forerun, a single volatile fraction, b.p. 96.0°-105.0° C./0.10 mm. Redistillation of this cut provided 8.9 g (41% yield) of ethyl-2-hydroxy-2-methyl-4-phenylbutynoate, as a colorless, viscous oil, b.p. 98.0°-101.0° C./0.05 mm.

Workup

  1. waitwas continued for an additional hour
  2. temperatureThe stirred solution was then heated
  3. customseparated into a two phase grey-black liquid
  4. temperatureAfter cooling
  5. additionthe two phase liquid was transferred under dry nitrogen to a 200 ml addition funnel
  6. customby flushing with two 15 ml portions of dry ether
  7. temperaturecooled to -20° C
  8. stirringThe mixture was stirred at -20° C. for 2 hours
  9. temperatureto warm to room temperature overnight
  10. stirringafter stirring for 5 minutes
  11. customthe phases were separated
  12. washthe combined organic phases were washed with three 75 ml portions of brine
  13. dry with materialdried over MgSO4
  14. filtrationAfter filtration and concentration at the stripper
  15. customto afford
  16. distillationRedistillation of this cut

Sources & evidence

ORD record
ord-242be574d73d42c79e5b62452ea37118
Source dataset
uspto-grants-1987_11
Patent number
US04704161

Reaction notes

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