Dichloromethane → 1-(tert-butoxycarbonyl)cyclopropanecarboxylic acid

At room temperature under shielded light, to N,N′-diisopropylcarbodiimide (99.75 g) was added copper(I) chloride (1.57 g), and then tert-butanol (83 ml) was added dropwise over 20 minutes, followed by stirring for 4 days. The supernatant (12.7 ml) was added to a dichloromethane solution (40 ml) of 1-(ethoxycarbonyl)cyclopropanecarboxylic acid (6.37 g), and heated at reflux for 3 hours. Hexane (50 ml) was added to the reaction solution, and the precipitate was filtered off. After the filtrate was concentrated under reduced pressure, a saturated aqueous sodium hydrogen carbonate solution was added to the residue, and extracted with dichloromethane. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. After hexane was added to the resulting residue, the precipitate was filtered off, and the filtrate was concentrated. The resulting residue was dissolved in tetrahydrofuran (25 ml), and 1 N aqueous sodium hydroxide solution (25 ml) was added, and stirred at room temperature overnight. After the reaction solution was concentrated under reduced pressure, 1 N aqueous sodium hydroxide solution (15 ml) was added to the residue, and washed with dichloromethane. A 10% aqueous citric acid solution was added to the aqueous layer to render it acidic, and extracted with dichloromethane. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford 1-(tert-butoxycarbonyl)cyclopropanecarboxylic acid (1.80 g).

1. temperatureheated
2. temperatureat reflux for 3 hours
3. filtrationthe precipitate was filtered off
4. concentrationAfter the filtrate was concentrated under reduced pressure
5. additiona saturated aqueous sodium hydrogen carbonate solution was added to the residue
6. extractionextracted with dichloromethane
7. washThe organic layer was washed with saturated sodium chloride solution
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated under reduced pressure
10. additionAfter hexane was added to the resulting residue
11. filtrationthe precipitate was filtered off
12. concentrationthe filtrate was concentrated
13. dissolutionThe resulting residue was dissolved in tetrahydrofuran (25 ml)
14. addition1 N aqueous sodium hydroxide solution (25 ml) was added
15. stirringstirred at room temperature overnight
16. concentrationAfter the reaction solution was concentrated under reduced pressure, 1 N aqueous sodium hydroxide solution (15 ml)
17. additionwas added to the residue
18. washwashed with dichloromethane
19. additionA 10% aqueous citric acid solution was added to the aqueous layer
20. extractionextracted with dichloromethane
21. washThe organic layer was washed with saturated sodium chloride solution
22. dry with materialdried over anhydrous sodium sulfate
23. concentrationconcentrated under reduced pressure

ORD record

ord-b07a04df900a43b686c0aaafdddca5cb

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729095B2