Methanol → (R)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanal

Temperature

-78 °C

To a solution of (R)-methyl 3-(tert-butyldimethylsilyloxy)-4-chlorobutanoate (27.9 g, 104.7 mmol) in CH2Cl2 was added dropwise DIBAL-H (120 mL, 1 M in toluene, 120 mmol) at −78° C. under N2 atmosphere. The mixture was stirred at −78° C. for 4 h. CH3OH (80 mL) was added slowly to the reaction mixture at −78° C. Then the temperature was warmed to room temperature gradually. The mixture was filtered and the cake was washed with CH2Cl2. The combined filtrates were concentrated under reduced pressure and purified by column chromatography (PE) to give (R)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanal (13 g, 60% over 2 steps). 1H NMR (300 MHz, CDCl3) δ 9.80 (t, J=1.6 Hz, 1H), 4.35-4.42 (m, 1H), 3.53 (dd, J=11.1 Hz, 4.8 Hz, 1H), 3.46 (dd, J=12 Hz, 6.3 Hz, 1H), 2.63-2.82 (m, 2H), 0.87 (s, 9H), 0.12 (s, 3H), 0.08 (s, 3H).

1. temperatureThen the temperature was warmed to room temperature gradually
2. filtrationThe mixture was filtered
3. washthe cake was washed with CH2Cl2
4. concentrationThe combined filtrates were concentrated under reduced pressure
5. custompurified by column chromatography (PE)

ORD record

ord-8432bf9474be46aaa01f9dc890b9d4d1

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962856B2