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

HRID 10372

Reaction equation

HRID 10372 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].BrCC1C=CC=C(C)C=1C(Br)=O.CC1C=CC=C(C)C=1C(OC)=O>CN1C(=O)CCC1.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 5

HCID 519028Methyl 2,6-dimethylbenzoateHCID 64327411,3-Cyclohexanediol, cis-HCID 10263795Methyl 2-(bromomethyl)-6-methylbenzoateHCID 219803072-(Bromomethyl)-6-methylbenzoyl bromideHCID 23665647Potassium tert-butoxide

Product 1

HCID 69207297Methyl 2-(cis-3-hydroxycyclohexyloxymethyl)-6-methylbenzoateYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
-5 °C

Procedure

500 g (4.3 mol) of cis-1,3-cyclohexanediol were dissolved in 5 l of NMP and admixed with 336 g (3.0 mol) of potassium tert-butoxide (KOtBu). The internal temperature rose to 28° C. The mixture was stirred for 30 min, then cooled to −5° C. and admixed dropwise with 370 g (approx. 94%, approx. 1.4 mol) of methyl 2-bromomethyl-6-methylbenzoate which may be prepared, for example, by methanolyzing 2-bromomethyl-6-methylbenzoyl bromide or by brominating methyl 2,6-dimethylbenzoate. The mixture was stirred for 30 min and then diluted with 5 l of water. After washing three times with 3 l of n-heptane each time and discarding the n-heptane solutions, the remaining aqueous phase was extracted four times with 2.5 l of MTBE each time. The combined MTBE phases were washed once with 5 l of water, dried over Na2SO4 and subsequently concentrated by evaporation under reduced pressure. 234 g of the desired compound were obtained as a yellowish oil and were used in the next reaction (for example an optical resolution) without further purification; 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. customrose to 28° C
  2. stirringThe mixture was stirred for 30 min
  3. washAfter washing three times with 3 l of n-heptane each time
  4. extractionthe remaining aqueous phase was extracted four times with 2.5 l of MTBE each time
  5. washThe combined MTBE phases were washed once with 5 l of water
  6. dry with materialdried over Na2SO4
  7. concentrationsubsequently concentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-80a2de2b1a184d3f92e129ddd5a674a8
Source dataset
uspto-grants-2006_08
Patent number
US07094795B2

Linked notes

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