Dimethyl Sulfate → 1,2,3-Trimethoxy-5-(1-methoxyprop-2-ynyl)benzene

HRID 532988

Reaction equation

HRID 532988 reaction equation
[H-].[Na+].[CH3:3]CCCC.[CH3:8][O:9][C:10]1[CH:11]=[C:12]([CH:20]([OH:23])[C:21]#[CH:22])[CH:13]=[C:14]([O:18][CH3:19])[C:15]=1[O:16][CH3:17].COS(OC)(=O)=O>C1COCC1.O>[CH3:19][O:18][C:14]1[CH:13]=[C:12]([CH:20]([O:23][CH3:3])[C:21]#[CH:22])[CH:11]=[C:10]([O:9][CH3:8])[C:15]=1[O:16][CH3:17]

Participants

7

Reactant 4

HCID 6497Dimethyl SulfateHCID 8003PentaneHCID 24758Sodium hydrideHCID 161103271-(3,4,5-Trimethoxyphenyl)-2-propyn-1-ol

Product 1

HCID 161103401,2,3-Trimethoxy-5-(1-methoxyprop-2-ynyl)benzeneYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a flame-dried 100 mL round-bottom flask was added NaH (0.240 mg, 6.0 mmol) that had been prewashed with pentane (3×15 mL) and dried. THF (48 mL) was added and the suspension cooled to 0° C. 1-(3,4,5-Trimethoxyphenyl)prop-2-yn-1-ol (1.11 g, 5.0 mmol) in THF (2.0 mL) was added dropwise and the reaction stirred at 0° C. for 25 min. Me2SO4 (0.571 mL, 6.0 mmol) was added and the reaction stirred at 0° C. for 20 min. Water (10 mL) was added, and the layers were separated. The aqueous layer was extracted with Et2O (20 mL). The combined organics were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash chromatography (SiO2, 20 g) using 10% EtOAc in hexanes as the eluent to afford 1,2,3-Trimethoxy-5-(1-methoxyprop-2-ynyl)benzene as a colorless oil (1.06 g, 90%): Rf=0.18 (4:1, Hex:EtOAc); 1H NMR (CDCl3) δ 6.75 (s, 2H), 5.01 (d, J) 2.2 Hz, 1H), 3.88 (s, 6H), 3.84 (s, 3H), 3.45 (s, 3H), 2.68 (d, J) 2.2 Hz, 1H); 13C NMR (CDCl3) δ 153.4, 138.2, 133.7, 104.4, 81.3, 76.0, 73.1, 61.0, 56.3, 56.2; HRFAB [M+Li] 243.1208 (calculated C13H16O4Li: 243.1209).

Workup

  1. customdried
  2. additionTHF (48 mL) was added
  3. stirringthe reaction stirred at 0° C. for 20 min
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with Et2O (20 mL)
  6. washThe combined organics were washed with brine (20 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography (SiO2, 20 g)

Sources & evidence

ORD record
ord-af2d523f0dc148639a6e3ac3d594c7ea
Source dataset
uspto-grants-2014_10
Patent number
US08853228B2

Linked notes

Loading…