Pyridine → HCID 68805934, compound

Temperature

0 °C

Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (3.8 g, 18 mmol) was dissolved in 150 mL dry diethyl ether under Ar, and the resulting solution was cooled in an ice water bath, while dry pyridine (8.6 mL, 106 mmol) was added, followed by the dropwise addition of oxalyl chloride (4.6 mL, 53 mmol). A precipitate formed immediately. The reaction was stirred vigorously at 0° C. for one hour, then at ambient temperature for one hour. 100 mL of diethyl ether were then added, and the solids wwere removed by filitration washing with diethyl ether. Concentrated the filtrates to an off-white oil. Redissolved oil in 50 mL dry DCM under Ar, cooled to 0° C., added 6 mL pyridine followed by 4-bromo-2-fluoroaniline (3.4 g, 17.7 mmol). The reaction was allowed to warm to ambient temperature, stirred for 3 hours then concentrated. Redissolved in 250 mL EtOAc, washed with 10% HCl (3×100 mL), brine (100 mL), dried with MgSO4, filtered and concentrated. Purified on a silica gel column eluted with 20% moving to 40% EtOAc in hexanes. Combined and concentrated pure fractions to yield title compound as a white solid. (3.2 g, 47%) APCI (AP−): 385.1, 387.1 (M−H)−.

1. additionwas added
2. customA precipitate formed immediately
3. waitat ambient temperature for one hour
4. customthe solids wwere removed by filitration
5. washwashing with diethyl ether
6. concentrationConcentrated the filtrates to an off-white oil
7. dissolutionRedissolved oil in 50 mL dry DCM under Ar
8. temperaturecooled to 0° C.
9. additionadded 6 mL pyridine
10. temperatureto warm to ambient temperature
11. stirringstirred for 3 hours
12. concentrationthen concentrated
13. dissolutionRedissolved in 250 mL EtOAc
14. washwashed with 10% HCl (3×100 mL), brine (100 mL)
15. dry with materialdried with MgSO4
16. filtrationfiltered
17. concentrationconcentrated
18. customPurified on a silica gel column
19. washeluted with 20%
20. concentrationconcentrated pure fractions

ORD record

ord-1889d13434a0484caaba733dd976af4d

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07030141B2