p-(Dimethoxymethyl)anisole → [(2R,4R)-2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-4-yl]methanol

HRID 1643419Notes

Reaction equation

HRID 1643419 reaction equation
[CH3:1][C:2]([CH3:9])([CH2:7][OH:8])[C@@H:3]([OH:6])[CH2:4][OH:5].CO[CH:12](OC)[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C(Cl)Cl>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([C@H:12]2[O:6][C@@H:3]([CH2:4][OH:5])[C:2]([CH3:9])([CH3:1])[CH2:7][O:8]2)=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 75140p-(Dimethoxymethyl)anisoleHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 10988310(R)-3,3-dimethylbutane-1,2,4-triol

Product 1

HCID 15858737[(2R,4R)-2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-4-yl]methanol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of compound obtained in Step A (5.6 g, 41.76 mmol) in dry CH2Cl2 (115 mL) was added p-methoxybenzaldehyde dimethyl acetal (11.42 g, 62.64 mmol) and pyridinium p-toluenesulfonate (2.1 g, 8.35 mmol). The mixture was heated at reflux for 18 h, then was cooled to room temperature and the reaction was quenched with saturated aqueous NaHCO3 solution (50 mL). The separated aqueous layer was extracted with Et2O (3×75 mL) and the combined extracts were washed with saturated aqueous NaCl solution (100 mL) and dried (MgSO4). Filtration and concentration of the filtrate in vacuo left a residue which was purified by flash chromatography (silica gel, gradient elution from 20% Et2O in hexanes to 40% Et2O in hexanes) to give the title compound as a colorless oil.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 18 h
  3. customthe reaction was quenched with saturated aqueous NaHCO3 solution (50 mL)
  4. extractionThe separated aqueous layer was extracted with Et2O (3×75 mL)
  5. washthe combined extracts were washed with saturated aqueous NaCl solution (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationFiltration and concentration of the filtrate in vacuo
  8. waitleft a residue which
  9. customwas purified by flash chromatography (silica gel, gradient elution from 20% Et2O in hexanes to 40% Et2O in hexanes)

Sources & evidence

ORD record
ord-2e6bb3faabad410b842ad13b8f45f478
Source dataset
uspto-grants-2012_02
Patent number
US08119806B2

Reaction notes

Loading…