Formaldehyde → HCID 69920989, compound

Temperature

-78 °C

Under ice cooling, diisopropylamine (0.296 g, 2.92 mmols) was added to a solution of n-butyl lithium (1.59 M/hexane solution, 2.79 mmols) in tetrahydrofuran (8 ml) and the mixture was stirred for 10 minutes. After cooling to −78° C., a solution of 3-ethoxycarbonyl-1-cyclobutanone (Compound e-1) (355.4 mg, 2.50 mmols) in tetrahydrofuran (3 ml) was dropwise added to the mixture, which was then stirred for 15 minutes. After the temperature was once elevated to 0° C., the mixture was stirred for 15 minutes and again cooled to −78° C. Hexamethylphosphoramide (535.8 mg, 2.99 mmols) was added to the system. After stirring for 5 minutes, a solution obtained by trapping formaldehyde subjected to cracking at 160° C. and trapped in diethyl ether of −78° C. was poured into the system through a needle. The reaction was terminated by adding hydrochloric acid and the insoluble matters were filtered off. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (50 ml, hexane:diethyl ether=1:1 to 1:2) to give Compound (e-2) (50.7 mg, yield: 12%).

1. stirringwas then stirred for 15 minutes
2. customwas once elevated to 0° C.
3. stirringthe mixture was stirred for 15 minutes
4. temperatureagain cooled to −78° C
5. stirringAfter stirring for 5 minutes
6. customa solution obtained
7. customto cracking at 160° C.
8. additionwas poured into the system through a needle
9. customThe reaction was terminated
10. additionby adding hydrochloric acid
11. filtrationthe insoluble matters were filtered off
12. concentrationThe filtrate was concentrated in vacuo
13. customThe residue was purified by silica gel column chromatography (50 ml, hexane:diethyl ether=1:1 to 1:2)
14. customto give Compound (e-2) (50.7 mg, yield: 12%)

ORD record

ord-684d2dd2c43d4476a4f68ada09f27e0e

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06384063B1