Diisopropylamine → tert-Butyl 1-[(4-chloro-3-nitrophenyl)(hydroxy)methyl]cyclopropanecarboxylate

Temperature

-78 °C

9.7 ml (24.3 mmol) of a 2.5 M solution of n-butyllithium in hexane were added dropwise to a solution, cooled to from −20° C. to −30° C., of 3.4 ml (24.3 mmol) of diisopropylamine in 20 ml of abs. THF. After the addition had ended, the mixture was stirred at from −20° C. to −30° C. for another 30 min. The mixture was then cooled to −78° C., and a solution of 2.53 g (17.8 mmol) of tert-butyl cyclopropanecarboxylate in 15 ml of abs. THF was added dropwise at this temperature. After 4 h at −78° C., a solution of 3 g (16.2 mmol) of 4-chloro-3-nitrobenzaldehyde in 15 ml of abs. THF was then added. The reaction mixture was slowly warmed to RT overnight and then allowed to stand at RT for three days, and saturated aqueous ammonium chloride solution was then added. The mixture was extracted with ethyl acetate and the organic phase was dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1→20:1). This gave 3.21 g of the target compound (60.6% of theory).

1. additionAfter the addition
2. waitAfter 4 h at −78° C.
3. temperatureThe reaction mixture was slowly warmed to RT overnight
4. waitto stand at RT for three days
5. extractionThe mixture was extracted with ethyl acetate
6. dry with materialthe organic phase was dried over magnesium sulphate
7. concentrationconcentrated under reduced pressure
8. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1→20:1)

ORD record

ord-7c7b4ad8ce8745eb86747ada47c2eec5

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018258B2