1,3-Cyclohexanediol → Methyl 2-(cis-3-hydroxycyclohexyloxymethyl)-6-methylbenzoate

HRID 1353163Notes

Reaction equation

HRID 1353163 reaction equation
[CH:1]1([OH:8])[CH2:6][CH2:5][CH2:4][CH:3]([OH:7])[CH2:2]1.C([Sn](=O)CCCC)CCC.Br[CH2:20][C:21]1[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[C:22]=1[C:23]([O:25][CH3:26])=[O:24].[F-].[Cs+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.CN(C)C=O.O>[OH:7][C@@H:3]1[CH2:4][CH2:5][CH2:6][C@H:1]([O:8][CH2:20][C:21]2[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[C:22]=2[C:23]([O:25][CH3:26])=[O:24])[CH2:2]1

Participants

9

Reactant 4

HCID 104331,3-CyclohexanediolHCID 25953Cesium fluorideHCID 61221Dibutyltin oxideHCID 10263795Methyl 2-(bromomethyl)-6-methylbenzoate

Product 1

HCID 69207297Methyl 2-(cis-3-hydroxycyclohexyloxymethyl)-6-methylbenzoate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

8.7 g of 1,3-cyclohexanediol and 12 g of dibutyltin oxide are dissolved in 600 ml of toluene and heated to the boil under reflux on a water separator. During the reaction, the reaction volume is reduced to half the original volume. After 4 hours, the reaction mixture is cooled to room temperature and 300 ml of dimethylformamide, 9.0 g of methyl 2-bromomethyl-6-methylbenzoate and 9.4 g of cesium fluoride are added. The mixture is stirred at room temperature for 12 hours. The reaction mixture is diluted by addition of ethyl acetate and washed with saturated sodium chloride solution. The organic phase is dried over magnesium sulfate, the solvent is reduced under reduced pressure and the residue is purified by flash chromatography on silica gel (n-heptane/ethyl acetate=50:1→1:2). This gives 6 g of methyl 2-(cis-3-hydroxycyclohexyloxymethyl)-6-methylbenzoate as an oil. C16H22O4 (278.35), MS(ESI): 279 (M+H+).

Workup

  1. temperatureheated to the boil
  2. customDuring the reaction
  3. washwashed with saturated sodium chloride solution
  4. dry with materialThe organic phase is dried over magnesium sulfate
  5. customthe residue is purified by flash chromatography on silica gel (n-heptane/ethyl acetate=50:1→1:2)

Sources & evidence

ORD record
ord-8ad8ffb33fb24f98a6ac7c5c0054746e
Source dataset
uspto-grants-2007_05
Patent number
US07220876B2

Reaction notes

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