3,5-Dimethoxytoluene → 1,3-Dimethoxy-5-methyl-2-(4-phenylbutyl)benzene

HRID 1875369Notes

Reaction equation

HRID 1875369 reaction equation
[Li]CCCC.[CH3:6][O:7][C:8]1[CH:9]=[C:10]([CH3:16])[CH:11]=[C:12]([O:14][CH3:15])[CH:13]=1.[C:17]1([CH2:23][CH2:24][CH2:25][CH2:26]Br)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1.C1(C)C=CC=CC=1>[CH3:15][O:14][C:12]1[CH:11]=[C:10]([CH3:16])[CH:9]=[C:8]([O:7][CH3:6])[C:13]=1[CH2:26][CH2:25][CH2:24][CH2:23][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 778443,5-DimethoxytolueneHCID 2596681-Bromo-4-phenylbutaneHCID 178418339Butyllithium

Product 1

HCID 592724161,3-Dimethoxy-5-methyl-2-(4-phenylbutyl)benzeneYield 1,347.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of nBuLi in hexanes (1.7 M, 14 mL, 24 mmol) was added over 15 min to a solution of 3,5-dimethoxytoluene (2.93 mL, 20 mmol) in THF (20 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 h then at room temperature for 3 h. The reaction was cooled to 0° C. and a solution of the 4-phenylbutylbromide (4.13 mL, 1.2 mmol) in toluene (15 mL) was added over 5 min. The reaction mixture was allowed to warm to room temperature and heated to 80° C. for 3-4 h. The reaction was quenched slowly with water and partitioned over Et2O (100 mL) and water (100 mL). The phases were separated and the aqueous phase was extracted with Et2O (3×100 mL). The pooled organics were washed with brine (120 mL), dried over Na2SO4, and concentrated under vacuum and the crude product was purified by flash chromatography (silica-gel, petroleum ether/EtOAc 200:1) to afford the product as a clear oil (4.6 g, 81%). 1H NMR (CDCl3): δ 1.53-1.67 (m, 4H), 2.31 (s, 3H), 2.60-2.64 (m, 4H), 3.76 (s, 6H), 6.34 (s, 2H), 7.13-7.22 (m, 5H).

Workup

  1. waitat room temperature for 3 h
  2. temperatureThe reaction was cooled to 0° C.
  3. temperatureto warm to room temperature
  4. temperatureheated to 80° C. for 3-4 h
  5. customThe reaction was quenched slowly with water
  6. custompartitioned over Et2O (100 mL) and water (100 mL)
  7. customThe phases were separated
  8. extractionthe aqueous phase was extracted with Et2O (3×100 mL)
  9. washThe pooled organics were washed with brine (120 mL)
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated under vacuum
  12. customthe crude product was purified by flash chromatography (silica-gel, petroleum ether/EtOAc 200:1)

Sources & evidence

ORD record
ord-82d0f208b6d24333ab40f83e0d124341
Source dataset
uspto-grants-2012_11
Patent number
US08309545B2

Reaction notes

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