Diisopropylamine → 1-(3,4-Dichlorophenyl)-2-pyridin-4-yl-ethane-1,2-diol

Temperature

-78 °C

To a stirring solution of diisopropylamine (14.9 g, 19.4 mL, 148 mmol) in tetrahydrofuran (500 mL) at -78° C. was added, dropwise, n-butyllithium (59 mL of a 2.5M solution in tetrahydrofuran). After ten minutes, a solution of 4-pyridylcarbinol t-butyldimethylsilyl ether (30 g, 134 mmol) in tetrahydrofuran (150 mL) was added dropwise and the temperature allowed to rise to -15° C. The solution was again cooled to -78° C. and a solution of 3,4-dichlorobenzaldehyde (25.9 g, 134 mmol) in tetrahydrofuran (150 mL) added dropwise. After the solution was allowed to warm to -20° C., it was poured into saturated aqueous sodium hydrogen carbonate (2 L). The aqueous layer was extracted with ethyl acetate (3×400 mL), the combined organic layers dried over anhydrous magnesium sulfate, filtered and concentrated at reduced pressure. The resulting oil was dissolved in tetrahydrofuran (400 mL) and to this solution was added tetrabutylammonium fluoride (148 mL of a 1.0M solution in tetrahydrofuran) dropwise. After ten minutes, the reaction mixture was concentrated at reduced pressure and the resulting oil chromatographed on silica gel, eluting with 95:5 dichloromethane:methanol to give the title compound as a mixture of diastereomeric diols as a foam (31.7 g) which was used without further purification.

1. waitAfter ten minutes
2. customto rise to -15° C
3. temperatureto warm to -20° C.
4. extractionThe aqueous layer was extracted with ethyl acetate (3×400 mL)
5. dry with materialthe combined organic layers dried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated at reduced pressure
8. dissolutionThe resulting oil was dissolved in tetrahydrofuran (400 mL) and to this solution
9. additionwas added tetrabutylammonium fluoride (148 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 chromatographed on silica gel
13. washeluting with 95:5 dichloromethane

ORD record

ord-206b8b64359e4ea9915d09486349a3ce

Source dataset

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05717100