Hydrochloric Acid → 4-Methoxy-3,5-dimethyl-1,1'-biphenyl

HRID 2222223Notes

Reaction equation

HRID 2222223 reaction equation
C([Li])(C)(C)C.[CH3:6][C:7]1[CH:12]=[C:11](Br)[CH:10]=[C:9]([CH3:14])[C:8]=1[O:15][CH3:16].I[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.Cl>C1COCC1.[Cl-].[Zn+2].[Cl-]>[CH3:6][C:7]1[CH:12]=[C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:10]=[C:9]([CH3:14])[C:8]=1[O:15][CH3:16]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11575IodobenzeneHCID 2786544-Bromo-2,6-dimethylanisoleHCID 178418306HCID 178418306, compound

Product 1

HCID 468699604-Methoxy-3,5-dimethyl-1,1'-biphenylYield 86%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

T-butyllithium (1.3M in pentane, 17.9 ml, 23.2 mmol) was added slowly to a solution of 2,6-dimethyl-4-bromo-methoxybenzene (2.5 g, 11.6 mmol) in anhydrous THF (50 ml) at −78° C. under an atmosphere of argon, then after 1 hour a solution of anhydrous zinc chloride (1.6 g, 11.7 mmol) in THF (40 ml) was added by cannula and the clear solution allowed to warm to room temperature and stir for 1 hr. This solution was then added by cannula to iodobenzene (2.37 g, 11.6 mmol) and bis(triphenylphosphine)palladium (II)chloride (81 mg, 116 μmol) in THF (40 ml) and allowed to stir overnight. The reaction was added to 1N HCl (150 ml) and extracted into dichloromethane (2×300 ml). The organic phase was washed with water (150 ml), brine (150 ml) and dried (Na2SO4). The crude product was concentrated and purified by chromatography on silica gel (100 g), eluent 10% dichloromethanelhexanes to give 2,6-dimethyl-4-phenyl-methoxybenzene (2.11 g, 9.9 mmol) in 86% yield. 1H nmr (CDCl3): δ=7.6-7.2 (m, 7H); 3.78 (s, 3H) and 2.37 (s, 6H). Boron tribromide (4.72 g, 19 mmol) was added dropwise to a solution of 2,6-dimethyl-4-phenyl-methoxybenzene (2.35 g, 11.1 mmol) in dichloromethane (45 ml) at −78° C. under argon, then the solution was allowed to warm to room temperature overnight. Ice/water (75 g) was added to quench the reaction, then the reaction was extracted with dichloromethane (2×200 ml). The organic layer was washed with water (50 ml), brine (50 ml) and dried (Na2SO4). Removal of the solvent gave 2,6-dimethyl-4-phenyl-phenol (2.15 g, 10.8 mmol) in 98% yield as a white solid, a single component by TLC Rf (0.13) eluent 4:1 dichloromethane/hexanes and 1H nmr. 1H nmr (CDCl3): δ=7.6-7.2 (m, 7H); 4.70 (s, 1H) and 2.37 (m, 6H).

Workup

  1. stirringto stir overnight
  2. extractionextracted into dichloromethane (2×300 ml)
  3. washThe organic phase was washed with water (150 ml), brine (150 ml)
  4. dry with materialdried (Na2SO4)
  5. concentrationThe crude product was concentrated
  6. custompurified by chromatography on silica gel (100 g), eluent 10% dichloromethanelhexanes

Sources & evidence

ORD record
ord-f15e29bf33204d65a030fb00c85b1d78
Source dataset
uspto-grants-2008_05
Patent number
US07371755B1

Reaction notes

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