Potassium Sodium Tartrate → (S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxy-N-(pyridin-2-yl)propanamide

Temperature

0 °C

Trimethylaluminium (7.60 mL, 15.20 mmol) was added to pyridin-2-amine (1.431 g, 15.20 mmol) in anhydrous toluene (30 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. (S)-Methyl 3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxypropanoate (Intermediate AD3) (2.2 g, 7.60 mmol) in anhydrous toluene (10 mL) was added and the resulting solution was allowed to warm to room temperature and then heated at 80° C. for 4 hours. The mixture was cooled to room temperature, neutralised with Rochelle salt in water (20%, 75 mL), diluted with water (50 mL) and extracted with EtOAc (2×50 mL). The organic phase was separated, washed with brine, dried over MgSO4, filtered and evaporated. The crude product was purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane to give impure product. This was shown to contain the starting amine so was re-purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM to afford the product (1.928 g, 72.2%).

1. temperatureto warm to room temperature
2. temperatureheated at 80° C. for 4 hours
3. temperatureThe mixture was cooled to room temperature
4. extractionextracted with EtOAc (2×50 mL)
5. customThe organic phase was separated
6. washwashed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customevaporated
10. customThe crude product was purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane
11. customto give impure product
12. customso was re-purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM

ORD record

ord-174eeb59356a4bbaa9d2e0a02dfa2d9b

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143263B2