Diisopropylamine → HCID 86669380, compound

To a solution of diisopropylamine (9.1 mL, 65 mmol) in 43 mL of THF was added n-BuLi (26 mL, 65 mmol) at 0° C. slowly (5 min). The mixture was stirred at 0˜5° C. for 30 min. After the mixture was cooled to −78° C. (10 min), Ethylcyclobutanecarboxylate (8 mL, 59.6 mmol, 1.1 eq.) was added dropwise and stirred at −78° C. for 30 min. The enolate was added into the solution of (S)-4-iodobutan-2-yl methanesulfonate 96 (15 g, 54 mmol) in 100 mL of THF at −78° C. Cooling bath was removed to allow the reaction to warm up to RT. After 30 min at RT, reaction was quenched by addition of water and extracted with EtOAc. The organic layer was washed with brine then dried over MgSO4, filtered and concentrated down. The residue was purified by silica gel chromatography first with (5% to 30% EtOAc in hexanes) then 100% DCM to (98% DCM/2% EtOAc) to provide 5.3 g (36% isolated yield) of (S)-ethyl 1-(3-(methylsulfonyloxy)butyl)cyclobutanecarboxylate 97.

1. additionwas added dropwise
2. stirringstirred at −78° C. for 30 min
3. temperatureCooling bath
4. customwas removed
5. customthe reaction
6. waitAfter 30 min at RT
7. customreaction
8. customwas quenched by addition of water
9. extractionextracted with EtOAc
10. washThe organic layer was washed with brine
11. dry with materialthen dried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated down
14. customThe residue was purified by silica gel chromatography first with (5% to 30% EtOAc in hexanes)

ORD record

ord-bd02575dc5144cc68601cfb78e384c15

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859776B2