Water → HCID 303980, compound

Temperature

-5 °C

In a 500 mL RBF, fit with dropping funnel and stir bar, under N2 was charged with Methylene chloride (100 mL) and 2,5-Norbornadiene (25 mL, 0.24 mol). The mixture was cooled in an ice/NaCl bath (ca. −5° C.). The dropping funnel was charged with Chlorosulfonyl Isocyanate (21.4 mL, 0.246 mol) and Methylene chloride and this mixture was added dropwise slowly to the reaction over about 1 hour. The mixture was held at −5° C. for about 1 hour further with stirring then warmed to room temp by removal of the ice bath. This warming occurred over about 2 h. The mixture was quenched with water (60 mL) and stirred for 10 min. The org layer was separated, washed with brine, dried (sodium sulfate) and concentrated to give a pale yellow oil. The pale yellow oil was dissolved in Methylene chloride (100 mL, 2 mol) and added dropwise to a −5° C. (Ice/NaCl bath) solution of Sodium sulfite (24.5 g, 0.194 mol), Methylene chloride (30 mL, 0.5 mol), and Water (70 mL, 4 mol) in a two neck 500 mL RBF. During the addition, the pH of the mixture was kept between 7 and 10 (monitor by pH paper) by addition of 10% NaOH. The addition took about 1 h. Following the complete addition, the pH was adjusted to 8.5 and the milky white solution was stirred for 1 h at −5° C. The mixture was diluted with about 400 mL of methylene chloride and the mixture stirred vigorously overnight. The stirred mixture was transferred to a 1 L separatory funnel and the layers separated. The aq was extracted 2× further with dichloromethane (200 mL each) and the combined organics washed with brine, dried (MgSO4), filtered through a bed of Celite and concentrated to give 3-Aza-tricyclo[4.2.1.0(2,5)]non-7-en-4-one a white solid. (21.6 g) (65% yield); MP: 94-97° C.

1. additionthis mixture was added dropwise slowly to the reaction over about 1 hour
2. stirringfurther with stirring
3. waitThis warming occurred over about 2 h
4. customThe mixture was quenched with water (60 mL)
5. stirringstirred for 10 min
6. customThe org layer was separated
7. washwashed with brine
8. dry with materialdried (sodium sulfate)
9. concentrationconcentrated
10. customto give a pale yellow oil
11. additionDuring the addition
12. additionThe addition
13. waittook about 1 h
14. additionthe complete addition
15. stirringthe milky white solution was stirred for 1 h at −5° C
16. stirringthe mixture stirred vigorously overnight
17. customThe stirred mixture was transferred to a 1 L separatory funnel
18. customthe layers separated
19. extractionThe aq was extracted 2× further with dichloromethane (200 mL each)
20. washthe combined organics washed with brine
21. dry with materialdried (MgSO4)
22. filtrationfiltered through a bed of Celite
23. concentrationconcentrated

ORD record

ord-2b18ead0084e42408405acbc68de0706

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148391B2