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

HRID 1373160Notes

Reaction equation

HRID 1373160 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.O.C(OCC)(=O)C.CN(C=O)C>[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, in a water separator, heated under reflux. 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 DMF, 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 NaCl solution. The organic phase is dried over magnesium sulfate, the solvent is removed 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-hydroxy-cyclohexyloxymethyl)-6-methylbenzoate as an oil. C16H22O4 (278.35), MS(ESI): 279 (M+H+).

Workup

  1. temperatureheated
  2. temperatureunder reflux
  3. customDuring the reaction
  4. washwashed with saturated NaCl solution
  5. dry with materialThe organic phase is dried over magnesium sulfate
  6. customthe solvent is removed under reduced pressure
  7. customthe residue is purified by flash chromatography on silica gel (n-heptane/ethyl acetate=50:1−>1:2)

Sources & evidence

ORD record
ord-96cfc8be71fa4212bce12dcd96bef022
Source dataset
uspto-grants-2007_01
Patent number
US07160911B2

Reaction notes

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