Diisopropylamine → 1-(3-Methoxyphenyl)-2-pyridin-4-ylethane-1,2-diol

Temperature

-20 °C

To a stirring solution of diisopropylamine (4.5 g, 5.8 mL, 44 mmol) in tetrahydrofuran (170 mL) at -78° C. was added n-butyllithium (17.7 mL of a 2.5M solution in tetrahydrofuran) dropwise. After ten minutes, a solution of 4-pyridylcarbinol t-butyldimethylsilyl ether (9.0 g, 40 mmol) in tetrahydrofuran (35 mL) was added dropwise, and the temperature allowed to rise to -15° C. The solution was recooled to -78° C. and to it was added a solution of 3-anisaldehyde (5.5 g, 4.9 mL, 40 mmol) in tetrahydrofuran (35 mL) dropwise. The solution was allowed to warm to -20° C. and poured into saturated aqueous sodium hydrogen carbonate (300 mL). The aqueous layer was extracted with ethyl acetate (3×200 mL) and the organic layers were combined, dried over anhydrous magnesium sulfate, filtered and concentrated at reduced pressure. The resulting oil was dissolved in tetrahydrofuran (120 mL) and to this solution was added tetrabutylammonium fluoride (48 mL of a 1.0M solution in tetrahydrofuran) dropwise. After ten minutes, the reaction mixture was concentrated at reduced pressure and the resulting oil was chromatographed on silica gel eluting with 97:3 ethyl acetate:methanol to give a mixture of diastereomeric diols as a foam (8.5 g) which was used without further purification.

1. waitAfter ten minutes
2. customto rise to -15° C
3. customwas recooled to -78° C. and to it
4. extractionThe aqueous layer was extracted with ethyl acetate (3×200 mL)
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated at reduced pressure
8. dissolutionThe resulting oil was dissolved in tetrahydrofuran (120 mL) and to this solution
9. additionwas added tetrabutylammonium fluoride (48 mL of a 1.0M solution in tetrahydrofuran) dropwise
10. waitAfter ten minutes
11. concentrationthe reaction mixture was concentrated at reduced pressure
12. customthe resulting oil was chromatographed on silica gel eluting with 97:3 ethyl acetate
13. custommethanol to give
14. customwas used without further purification

ORD record

ord-ea383873bab343559b4d2f08c64524a2

Source dataset

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05717100