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

HRID 1968698Notes

Reaction equation

HRID 1968698 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-ff9bba336a7f44cd82e41db85d46b16a
Source dataset
uspto-grants-2013_04
Patent number
US08426432B2

Reaction notes

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