Reaction #10478

Reaction equation

cis-1,3-cyclohexanediol

methyl 2,6-dimethylbenzoate

methyl 2-bromomethyl-6-methylbenzoate

acid bromide

2-bromomethyl-6-methylbenzoyl bromide

potassium tert-butoxide

→

desired compound

Yield 14.2%

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

Yield 14.2%

Solvents

methyl tert-butyl ether

Water

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred at 0–5° C. for 1 h
2. 2
   Temperatureheated to 20–23° C.
3. 3
   workup.WAITleft
4. 4
   workup.STIRRINGto stir overnight
5. 5
   workup.STIRRINGthe mixture was stirred vigorously
6. 6
   Otherthe phases were separated
7. 7
   Washthe organic phase was washed once more with water
8. 8
   Concentrationthe organic phase was concentrated under reduced pressure
9. 9
   OtherThe residue (4.6 g) was chromatographed on silica gel (1:1 ethyl acetate/n-heptane)

Procedure

10.0 g (86 mmol) of cis-1,3-cyclohexanediol were taken up in 150 ml of methyl tert-butyl ether (MTBE), admixed at approx. 20° C. with 6.72 g (59.9 mmol) of potassium tert-butoxide (KOtBu) and stirred. After about 30 minutes, the suspension was cooled to 5° C. and admixed dropwise with 7.4 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. The mixture was stirred at 0–5° C. for 1 h, heated to 20–23° C. and left to stir overnight. Water was added, the mixture was stirred vigorously, the phases were separated, the organic phase was washed once more with water and then the organic phase was concentrated under reduced pressure. The residue (4.6 g) was chromatographed on silica gel (1:1 ethyl acetate/n-heptane). 1.2 g of the desired compound were 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), 1.82 (m, 1H), 2.05 (m, 1H), 2.34 (s, 3H), 3.46 (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