1-Bromo-2,4-bis(methoxymethoxy)benzene → 4-(4-{[tert-Butyl(dimethyl)silyl]oxy}phenyl)-1-[2,4-bis(methoxymethoxy)phenyl]cyclohexanol

Temperature

-78 °C

A round bottomed flask equipped with magnetic stirrer was charged with 1-bromo-2,4-bis(methoxymethoxy)benzene (277 mg, 1.00 mmol) and anhydrous tetrahydrofuran (5 ml). The stirred solution was cooled to −78° C. and N,N,N′N′-tetramethylethylene diamine (0.32 ml, 2.10 mmol) was added followed by dropwise addition of n-butyl lithium (0.88 ml, 2.10 mmol, 2.40M solution in cyclohexanes). The resulting solution was stirred for 40 min at −78° C., then 4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)cyclohexanone (304 mg, 1.00 mmol) was added via syringe as a solution in anhydrous tetrahydrofuran (2 ml) and the reaction mixture stirred for 30 min at −78° C., then allowed to warm to room temperature over 3 hr. The reaction was quenched with aqueous hydrochloric acid (5 ml, 0.10M), then poured into a separating funnel containing ethyl acetate (50 ml) and water (10 ml). The layers were separated and the aqueous phase extracted with ethyl acetate (3×5 ml). The combined organic layers were washed with brine (10 ml), dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting oil was purified via flash column chromatography (SiO2, ethyl acetate/petroleum ether, 3:7, v/v) furnishing the title compound as a white solid (127 mg, 25%) and a mixture of diastereoisomers. δH(CDCl3) 0.19 (6H, s), 0.98 (6H, s), 1.63 (2H, m), 1.84 (2H, m), 1.96 (2H, m), 2.56 (2H, m), 2.70 (1H, m), 3.48 (3H, s), 3.49 (3H, s), 3.85 (1H, s), 5.15 (2H, s), 5.24 (2H, s), 6.68 (1H, dd), 6.73 (2H, d), 6.85 (1H d), 7.05 (2H, d), 7.33 (1H, d).

1. customA round bottomed flask equipped with magnetic stirrer
2. stirringthe reaction mixture stirred for 30 min at −78° C.
3. temperatureto warm to room temperature over 3 hr
4. customThe reaction was quenched with aqueous hydrochloric acid (5 ml, 0.10M)
5. additionpoured into a separating funnel
6. additioncontaining ethyl acetate (50 ml) and water (10 ml)
7. customThe layers were separated
8. extractionthe aqueous phase extracted with ethyl acetate (3×5 ml)
9. washThe combined organic layers were washed with brine (10 ml)
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe resulting oil was purified via flash column chromatography (SiO2, ethyl acetate/petroleum ether, 3:7, v/v)

ORD record

ord-c4d16bab3063400284acca2e75c165e8

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06933319B2