Reaction #85096

Reaction equation

magnesium

(bromomethyl)cyclobutane diethyl ether

ethyl glyoxylate

iodine

(bromomethyl)cyclobutane

→

Ethyl 3-cyclobutyl-2-hydroxypropanoate

Solvents

diethyl ether

diethyl ether

Conditions

Workup

1. 1
   workup.STIRRINGthe reaction was stirred for 5 min (until the reaction
2. 2
   workup.ADDITIONis added dropwise over a further 10 min
3. 3
   workup.STIRRINGThe reaction mixture was stirred
4. 4
   Temperatureunder reflux for 1 h
5. 5
   workup.STIRRINGThe reaction mixture was stirred at RT for 1 h
6. 6
   Othercarefully quenched to pH 7 with 20 ml of a potassium citrate/citric acid solution (pH 5)
7. 7
   OtherAfter phase separation
8. 8
   Extractionthe aqueous phase was extracted with diethyl ether
9. 9
   DryingThe combined organic phases were dried (sodium sulphate)
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated under reduced pressure
12. 12
    OtherThe residue was purified by flash chromatography (silica gel 50, mobile phase: cyclohexane/ethyl acetate 20%-33%)

Procedure

359 mg (14.8 mmol, 1.1 eq.) of magnesium turnings were covered with diethyl ether and etched by addition of a small piece of iodine for 3-4 min. Under argon and at RT, 5 ml of a solution of 2.0 g (13.4 mmol) of (bromomethyl)cyclobutane in 30 ml of diethyl ether were added with stirring to this mixture, the reaction was stirred for 5 min (until the reaction is initiated) and the remainder of the (bromomethyl)cyclobutane/diethyl ether solution is added dropwise over a further 10 min. The reaction mixture was stirred under reflux for 1 h, cooled under a stream of argon and, with ice-water cooling, added dropwise to a solution of 2.4 ml (12.1 mmol, 0.9 eq.) of ethyl glyoxylate (50% in toluene). The reaction mixture was stirred at RT for 1 h, carefully quenched to pH 7 with 20 ml of a potassium citrate/citric acid solution (pH 5) and then adjusted to pH 4-5 with aqueous hydrochloric acid (1N). After phase separation, the aqueous phase was extracted with diethyl ether. The combined organic phases were dried (sodium sulphate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel 50, mobile phase: cyclohexane/ethyl acetate 20%-33%). Yield: 110 mg (purity 94%, 5% of theory)

Source