Methyl iodide → 4-Methoxymethylcyclohexanemethanol

HRID 1975308Notes

Reaction equation

HRID 1975308 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][CH:6]([CH2:9][OH:10])[CH2:5][CH2:4]1.[H-].[Na+].[CH3:13]I.[NH4+].[Cl-]>CN(C=O)C.CCCCCC.C(OCC)(=O)C>[CH3:13][O:1][CH2:2][CH:3]1[CH2:8][CH2:7][CH:6]([CH2:9][OH:10])[CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 77351,4-CyclohexanedimethanolHCID 24758Sodium hydrideHCID 25517Ammonium Chloride

Product 1

HCID 199387834-MethoxymethylcyclohexanemethanolYield 32.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

1,4-bis(Hydroxymethyl)cyclohexane (5 g, 0.0347 mol), cis/trans mixture 1:3, in anhydrous DMF (20 cm3) was added dropwise to NaH (1.6 g, 0.0366 mol, 55%) washed with hexane, under atmosphere of nitrogen. The mixture was stirred at room temperature for 1/2 h, then CH3I (5 g, 0.0352 mol) dissolved in DMF (20 cm3) was added dropwise. After the addition was complete the solution was stirred at room temperature for 2 h; NH4Cl solution was added then thoroughly extracted with ether, to which Na2SO4 was added and dried under reduced pressure. Chromatography on silica gel eluting with hexane/ethyl acetate (55/45) gave 4-methoxymethyl-cyclohexylmethanol (1.8 g, 0.0113 mol) out of 4.1 g of residue. Such compound was dissolved in ether (10 cm3), cooled to -70° C. and was added dropwise with PBr3 (1.2 g, 0.0044 mol). After the addition was complete the solution was stirred to room temperature for 2 h, was extracted with ether and cautiously added with satured NaHCO3 solution. After the two layers were separated, the organic phase was added with Na2SO4 and dried under reduced pressure. Chromatography on silica gel eluting with hexane gave 4-methoxymethyl cyclohexylmethyl bromide, cis trans mixture 1 3. Such product was employed in the example 8.

Workup

  1. washwashed with hexane, under atmosphere of nitrogen
  2. additionwas added dropwise
  3. additionAfter the addition
  4. stirringwas stirred at room temperature for 2 h
  5. extractionthen thoroughly extracted with ether, to which Na2SO4
  6. additionwas added
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-8cf0704c9151439ba6f55a95eb414891
Source dataset
uspto-grants-1994_02
Patent number
US05286725

Reaction notes

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