Reaction #89617

Reaction equation

(6-Methyl-cyclohex-3-enyl)-methanol

sodium amide

Bromomethyl-cyclopropane

→

4-cyclopropylmethoxymethyl-5-methyl-cyclohexene

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   Temperatureheated
2. 2
   workup.WAITThe reaction mixture was aged for a half-hour
3. 3
   Otherwas then fed for over 2 hours at the reflux temperature
4. 4
   OtherA sample the reaction mixture was quenched in isopropyl alcohol
5. 5
   Otherwas aged for a total of 6 hours
6. 6
   TemperatureThe reaction mixture was then cooled to 10° C.
7. 7
   Otherquenched with isopropyl alcohol (100 mL), water (1 L), and toluene (500 mL)
8. 8
   Washwashed with sodium carbonate solution (5%, 500 mL) in a separatory funnel
9. 9
   workup.DISTILLATIONDistillation of the resulting mixture

Procedure

A reaction flask was charged with tetrahydrofuran (THF, 500 mL) and sodium amide (NaNH2, 100 g, 2.6 mol) and heated to reflux (˜65° C.). (6-Methyl-cyclohex-3-enyl)-methanol (300 g, 2.3 mol) was fed in. The reaction mixture was aged for a half-hour. Bromomethyl-cyclopropane (526 g, 3.9 mol) was then fed for over 2 hours at the reflux temperature. The reaction was monitored by gas chromatography. A sample the reaction mixture was quenched in isopropyl alcohol, water, and toluene. After the feed of bromomethyl-cyclopropane was completed, the reaction was aged for a total of 6 hours. The reaction mixture was then cooled to 10° C. and quenched with isopropyl alcohol (100 mL), water (1 L), and toluene (500 mL). On the work-up, the reaction mixture was acidified with HCl (300 mL) and washed with sodium carbonate solution (5%, 500 mL) in a separatory funnel followed with warm H2O until the pH was neutral. Distillation of the resulting mixture provided the product 4-cyclopropylmethoxymethyl-5-methyl-cyclohexene.

Source