Isopropanol → HCID 69203609, compound

HRID 2378288Notes

Reaction equation

HRID 2378288 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH2:11][CH3:12])[CH:3]=1.C([Li])CCC.[CH2:18]([O:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[O:34][CH3:35])[CH:29]=[O:30])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O)(C)C>C1COCC1.O>[CH2:18]([O:25][C:26]1[CH:27]=[C:28]([CH:29]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH2:11][CH3:12])[CH:3]=2)[OH:30])[CH:31]=[CH:32][C:33]=1[O:34][CH3:35])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 806713-Benzyloxy-4-methoxybenzaldehydeHCID 217726904-Bromo-2-ethoxy-1-methoxybenzeneHCID 178418339Butyllithium

Product 1

HCID 69203609HCID 69203609, compoundYield 89.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A stirred mixture of 4-bromo-2-ethoxy-1-methoxy-benzene (5.25 g, 22.7 mmol) and dry THF (50 mL) was cooled to −78° C., evacuated and refilled with nitrogen for 10 cycles. To this clear solution was slowly added n-butyllithium (9.1 mL, 22.7 mmol) and stirred for 20 min. Then a mixture of 3-benzyloxy-4-methoxy-benzaldehyde (5.0 g, 20.6 mmol) in dry THF (20 mL) was added and stirred for 1 hour at −78° C. The mixture was quenched with isopropanol (9.4 mL, 248 mmol) and added water (50 mL). The mixture was extracted with EtOAc (3×80 mL). The combined organic phases were washed with water (2×80 mL), dried over MgSO4 and concentrated to oil, which was purified by flash column chromatography (EtOAc/Hexane) to give (3-benzyloxy-4-methoxy-phenyl)-(3-ethoxy-4-methoxy-phenyl)-methanol as an off-white solid (7.26 g, 89% yield): 1H NMR (CDCl3) δ 1.43 (t, J=7 Hz, 3H, CH2CH3), 2.09 (d, J=3 Hz, 1H, OH), 3.86 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 4.00 (q, J=7 Hz, 2H, CH2CH3), 5.10 (s, 2H, CH2), 5.68 (d, J=3 Hz, 1H, CH), 6.80-6.92 (m, 6H, Ar), 7.26-7.41 (m, 5H, Ar). The product was used in the next step without further purification.

Workup

  1. customevacuated
  2. additionrefilled with nitrogen for 10 cycles
  3. additionwas added
  4. stirringstirred for 1 hour at −78° C
  5. extractionThe mixture was extracted with EtOAc (3×80 mL)
  6. washThe combined organic phases were washed with water (2×80 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated to oil, which
  9. customwas purified by flash column chromatography (EtOAc/Hexane)

Sources & evidence

ORD record
ord-9984b803ca2b484b94669bdfc03aeff2
Source dataset
uspto-grants-2008_12
Patent number
US07470723B2

Reaction notes

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