Formaldehyde → Formaldehyde

Temperature

-15 °C

A solution of LDA (280 mmol) was prepared by addition of n-BuLi (1.6 M in THF, 175 mL, 280 mmol) to a solution of diisopropylamine (39.3 mL, 280 mmol) in THF (400 mL) at −40° C. and stirring the resulting solution at −15° C. for 30 min. Subsequently the solution was cooled down to −78° C. and a solution of the starting material (50.0 g, 233 mmol) in THF (400 mL) was added dropwisely. After 1 h, gaseous formaldehyde (1.05 mol), which was prepared by heating paraformaldehyde (31.5 g, 1.05 mol) in a separate flask connected by a polyethylene tube to the reaction flask, was passed at −78° C. through this solution over a period of 1 h. After being stirred at −78° C. for additional 30 min and allowed to reach 25° C. over 3 h, the reaction was quenched (saturated aqueous NH4Cl) and extracted (3×EtOAc). The combined organic layers were washed (brine), dried (Na2SO4), and concentrated under reduced pressure. Flash chromatography (SiO2, 30-60% EtOAc/hexanes, gradient elution) gave the product as a pale yellow oil.

1. temperatureSubsequently the solution was cooled down to −78° C.
2. waitAfter 1 h
3. customconnected by a polyethylene tube to the reaction flask
4. waitwas passed at −78° C. through this solution over a period of 1 h
5. stirringAfter being stirred at −78° C. for additional 30 min
6. waitto reach 25° C. over 3 h
7. customthe reaction was quenched (saturated aqueous NH4Cl)
8. extractionextracted (3×EtOAc)
9. washThe combined organic layers were washed (brine)
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated under reduced pressure
12. washFlash chromatography (SiO2, 30-60% EtOAc/hexanes, gradient elution)

ORD record

ord-6e459ca4f32b4697a7c8fba2c747b0f3

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772296B2