Reaction #10477

Reaction equation

cis-1,3-cyclohexanediol

potassium tert-butoxide

methyl 2,6-dimethylbenzoate

methyl 2-bromomethyl-6-methylbenzoate

→

desired compound

Yield 14.2%

racemic methyl cis-2-(3-hydroxycyclohexyloxymethyl)-6-methylbenzoate

Yield 14.2%

Solvents

methyl tert-butyl ether

Water

dimethoxyethane

Conditions

Workup

1. 1
   workup.ADDITIONare added dropwise
2. 2
   workup.STIRRINGThe mixture is stirred at 5–10° C. for 1 h
3. 3
   Otherat 20–23° C.
4. 4
   Otherovernight
5. 5
   workup.STIRRINGthe mixture is stirred vigorously
6. 6
   Otherthe phases are separated
7. 7
   Washthe aqueous phase is washed once more with MTBE
8. 8
   Concentrationthe combined organic phases are concentrated under reduced pressure
9. 9
   OtherThe residue is chromatographed on silica gel (1:1 ethyl acetate/n-heptane)

Procedure

5 g (42.8 mmol) of cis-1,3-cyclohexanediol were dissolved in 50 ml of dimethoxyethane (DME), admixed at 20–23° C. with 3.36 g (30 mmol) of potassium tert-butoxide (KOtBu) and stirred. After about 30 minutes, the mixture is cooled to 5° C. and 3.7 g (approx. 50%) of methyl 2-bromomethyl-6-methylbenzoate, which may be prepared, for example, by methanolyzing the acid bromide (2-bromomethyl-6-methylbenzoyl bromide) or by brominating methyl 2,6-dimethylbenzoate, are added dropwise. The mixture is stirred at 5–10° C. for 1 h and then at 20–23° C. overnight. Water and methyl tert-butyl ether (MTBE) are added, the mixture is stirred vigorously, the phases are separated, the aqueous phase is washed once more with MTBE and the combined organic phases are concentrated under reduced pressure. The residue is chromatographed on silica gel (1:1 ethyl acetate/n-heptane). 600 mg of the desired compound are obtained as a light yellow oil, 1H NMR (CDCl3), δ =1.27 (m, 1H), 1.45 (m, 1H), 1.55 (m, 1H), 1.74 (m, 1H), 1.83 (m, 1H), 2.05 (m, 1H), 2.34 (s, 3H), 3.47 (m, 1H), 3.72 (m, 1H), 3.91 (s, 3H), 4.58 (dd, 2H), 7.15 (d, 1H), 7.20 (d, 2H), 7.27 (m, 1H).

Source