2-Bromopyridine → (S)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(pyridin-2-yl)ethyl)-2-methylpropane-2-sulfinamide

To a solution of toluene (40 mL) cooled to −78° C. was added butyl lithium (1.6 M in hexanes, 5.57 mL, 13.9 mmol) at a rate such that the internal temperature did not exceed −50° C., and the reaction stirred until the internal temperature returned to −78° C. 2-Bromopyridine (1.20 mL, 12.7 mmol) in toluene (4 mL) was added to the reaction mixture at a rate such that the temperature did not exceed −65° C. The reaction was stirred at −78° C. for 1 hour. To the reaction was added (S,E)-N-(2-(tert-butyldimethylsilyloxy)ethylidene)-2-methylpropane-2-sulfinamide (3.58 g, 13.9 mmol) in toluene (20 mL) at a rate such that the internal temperature did not exceed −60° C. The reaction was stirred at −78° C. for 2 hours. To the −78° C. solution was added brine (50 mL) and the mixture was partitioned between EtOAc/water (300 mL total). The organic layer was washed with brine (50 mL), dried over MgSO4 and concentrated in vacuo. The crude material was chromatographed using 40% EtOAc/DCM as eluent to yield (S)—N—((S)-2-(tert-butyldimethylsilyloxy)-1-(pyridin-2-yl)ethyl)-2-methylpropane-2-sulfinamide (2.1 g, 46.7%).

1. customdid not exceed −50° C.
2. customreturned to −78° C
3. customdid not exceed −65° C
4. stirringThe reaction was stirred at −78° C. for 1 hour
5. customdid not exceed −60° C
6. stirringThe reaction was stirred at −78° C. for 2 hours
7. customthe mixture was partitioned between EtOAc/water (300 mL total)
8. washThe organic layer was washed with brine (50 mL)
9. dry with materialdried over MgSO4
10. concentrationconcentrated in vacuo
11. customThe crude material was chromatographed

ORD record

ord-f884bb8a860d4e29a8e96fe8eaaf7c15

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08865726B2