Triethylamine → Methyl 5-chloro-2-(3-(3-fluorophenyl)-3-hydroxyazetidin-1-yl)nicotinate

To a cooled (0° C.) solution of tert-butyl 3-(3-fluorophenyl)-3-hydroxyazetidine-1-carboxylate (D28) (100 mg, 0.374 mmol) in dichloromethane (0.5 ml), a mixture 3:1 of trifluoroacetic acid/dichloromethane (1 ml) was added and the mixture was stirred 30 min at room temperature. The residue obtained after solvent evaporation was dissolved in a mixture 3:1 of tetrahydrofuran/methanol (1 ml) and triethylamine (0.156 ml, 1.122 mmol) was added followed by addition of methyl 2,5-dichloronicotinate (77.32 mg, 0.374 mmol). The resulting mixture was heated 15 h at 60° C. After solvent evaporation the residue was taken in NH4Cl sat. sol. (10 ml) and the resulting mixture was extracted with ethylacetate (2×10 ml). The residue obtained after solvet evaporation was purified by SPE-Si cartridge (5 g) eluting with a mixture cyclohexane/ethylacetate from 100/0 to 90:10. Collected fractions, after solvent evaporation afforded the title compound (D80) (71.4 mg)

1. customThe residue obtained
2. customafter solvent evaporation
3. additionwas added
4. temperatureThe resulting mixture was heated 15 h at 60° C
5. customAfter solvent evaporation the residue
6. extractionthe resulting mixture was extracted with ethylacetate (2×10 ml)
7. customThe residue obtained
8. customafter solvet evaporation
9. customwas purified by SPE-Si cartridge (5 g)
10. washeluting with a mixture cyclohexane/ethylacetate from 100/0 to 90:10
11. customCollected fractions, after solvent evaporation

ORD record

ord-a2dc3b146bfc435393ab564a73b8fb2f

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08828987B2