Tetrahydrofuran → 3,5-Dimethyl-4-(3'-isopropyl-4'-methoxybenzylhydroxy) anisole

HRID 1872422Notes

Reaction equation

HRID 1872422 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([CH:10]([CH3:12])[CH3:11])[CH:3]=1.C([Li])(C)(C)C.[CH3:18][C:19]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23]([CH3:29])[C:20]=1C=O.C1C[O:33][CH2:32]C1>CCOCC>[CH3:29][C:23]1[CH:24]=[C:25]([O:27][CH3:28])[CH:26]=[C:19]([CH3:18])[C:20]=1[O:33][CH2:32][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([CH:10]([CH3:12])[CH3:11])[CH:3]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8167794-Methoxy-2,6-dimethylbenzaldehydeHCID 146987944-Bromo-2-isopropyl-1-methoxybenzeneHCID 178418306HCID 178418306, compound

Product 1

HCID 542724073,5-Dimethyl-4-(3'-isopropyl-4'-methoxybenzylhydroxy) anisoleYield 73%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

To 4-bromo-2-isopropylanisole (a compound of Formula 3 from Example 2) (12 g, 52.4 mmol) in 300 mL of THF at -78° C. was added 68 mL of tert-butyllithium (1.7 M in pentane). The reaction mixture was stirred for 10 min at -78° C. and then 2,6-dimethyl-4-methoxybenzaldehyde (a compound of Formula 6 from Example 4) (8.6 g, 52.4 mmol) was added. The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature, diluted with 150 mL of ether, washed with 150 mL of water, acidified with 1N HCl, and washed with 5×50 mL of brine. The organic portion was dried (MgSO4), filtered, and evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 95:5 hexane/ethylacetate) to yield 3,5-dimethyl-4-(3'-isopropyl-4'-methoxybenzylhydroxy) anisole (7) (12 g, 38.2 mmol, 73%) as an oil; 1HNMR (CDCl3) δ1.2 (dd, 6H), 2.27 (s, 6H), 3.30 (heptet, 1H), 3.80 (s, 6H), 6.26 (s, 1H), 6.59 (s, 2H), 6.76 (d, 1H), 6.89 (d, 1H), 7.24 (s, 1H).

Workup

  1. stirringThe reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature
  2. washwashed with 150 mL of water
  3. washwashed with 5×50 mL of brine
  4. dry with materialThe organic portion was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give the crude product, which
  8. customwas purified by flash column chromatography (silica gel, 95:5 hexane/ethylacetate)

Sources & evidence

ORD record
ord-39804862e3244596b7746aad931502d1
Source dataset
uspto-grants-2000_08
Patent number
US06107517

Reaction notes

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