Methyl 2,6-dimethylbenzoate → Methyl 2-(cis-3-hydroxycyclohexyloxymethyl)-6-methylbenzoate

HRID 10381

Reaction equation

HRID 10381 reaction equation
[C@H:1]1([OH:8])[CH2:6][CH2:5][CH2:4][C@@H:3]([OH:7])[CH2:2]1.CC(C)([O-])C.[K+].Br[CH2:16][C:17]1[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[C:18]=1[C:19]([O:21][CH3:22])=[O:20].CC1C=CC=C(C)C=1C(OC)=O>C(COC)OC.C(OC)(C)(C)C.O>[OH:7][C@@H:3]1[CH2:4][CH2:5][CH2:6][C@H:1]([O:8][CH2:16][C:17]2[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[C:18]=2[C:19]([O:21][CH3:22])=[O:20])[CH2:2]1

Participants

8

Reactant 4

HCID 519028Methyl 2,6-dimethylbenzoateHCID 64327411,3-Cyclohexanediol, cis-HCID 10263795Methyl 2-(bromomethyl)-6-methylbenzoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 69207297Methyl 2-(cis-3-hydroxycyclohexyloxymethyl)-6-methylbenzoateYield 14.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
5 °C

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).

Workup

  1. additionare added dropwise
  2. stirringThe mixture is stirred at 5–10° C. for 1 h
  3. customat 20–23° C.
  4. customovernight
  5. stirringthe mixture is stirred vigorously
  6. customthe phases are separated
  7. washthe aqueous phase is washed once more with MTBE
  8. concentrationthe combined organic phases are concentrated under reduced pressure
  9. customThe residue is chromatographed on silica gel (1:1 ethyl acetate/n-heptane)

Sources & evidence

ORD record
ord-39f6c4bd24b6470583618751582d3aed
Source dataset
uspto-grants-2006_08
Patent number
US07094795B2

Linked notes

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