4-Methoxy-2-methylbenzaldehyde → HCID 66643057, compound

HRID 1171011Notes

Reaction equation

HRID 1171011 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([CH:10]([CH3:12])[CH3:11])[C:3]=1[CH3:13].[Li]CCCC.[CH3:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=[O:26])=[C:23]([CH3:29])[CH:22]=1>C1COCC1>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([CH:25]([C:24]2[CH:27]=[CH:28][C:21]([O:20][CH3:19])=[CH:22][C:23]=2[CH3:29])[OH:26])=[C:3]([CH3:13])[C:4]=1[CH:10]([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 2832854-Methoxy-2-methylbenzaldehydeHCID 66642817HCID 66642817, compound2×HCID 178418339Butyllithium

Product 1

HCID 66643057HCID 66643057, compoundYield 116.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirring solution of 1-bromo-3-iso-propyl-4-methoxy-2-methyl-benzene (compound 7-16, step c; 0.7 g, 2.88 mmol) in THF (20 mL) at −78° C. was added n-BuLi (1.6 mL, 2.5 M in hexanes). The mixture was stirred at −78° C. for 1 hr and 4-methoxy-2-methyl-benzaldehyde (0.37 mL, 2.74 mmol) was added. The reaction mixture was stirred at −78° C. for 1 hr, allowed to warm to room temperature and stirred for 1 hr. The reaction mixture was quenched with saturated NH4Cl and diluted with diethyl ether. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to afford crude (4′-methoxy-3′-iso-propyl-2′-methylphenyl)-(4-methoxy-2-methylphenyl)-methanol as a light yellow oil (1.0 g, 100%). This crude oil was dissolved into EtOAc (25 mL) and AcOH (5 mL) and Pd/C (0.1 g) was added. After stirring at rt for 6 hours, the reaction mixture was filtered through the Celite and concentrated under reduced pressure to afford crude 4-(4′-methoxy-2′-methyl-3′-iso-propylbenzyl)-3-methyl-anisole as a yellow oil (0.8 g, 93%): 1H NMR (300 MHz, DMSO-d6): δ 6.88-6.80 (m, 5 H), 3.77 (s, 2 H), 3.74 (s, 3 H), 3.71 (s, 3 H), 3.34 (m, 1 H), 2.22 (s, 3 H), 2.14 (s, 3 H), 1.28 (d, J=6.9 Hz, 6 H); TLC conditions: Uniplate silica gel, 250 microns; Mobile phase=8% ethyl acetate in hexanes; Rf=0.56.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 1 hr
  2. temperatureto warm to room temperature
  3. stirringstirred for 1 hr
  4. customThe reaction mixture was quenched with saturated NH4Cl
  5. additiondiluted with diethyl ether
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d339b15783af4f47877ffacc25d1dc83
Source dataset
uspto-grants-2010_11
Patent number
US07829552B2

Reaction notes

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