Acetic Acid → [2-(2-Fluoro-phenyl)-ethyl]-[2-(2-hydroxy-ethyl)-benzyl]-carbamic acid tert-butyl ester

2-(2-Fluoro-phenyl)-ethylamine (0.34 mL) was added to a solution of iso-chroman-1-ol (0.26 g) and acetic acid (0.1 mL) in methanol (5 mL). After stirring for 1 hour, sodium cyanoborohydride (0.17 g) was added and stirred for 18 hours. A few drops of 0.880 ammonia solution was added and the resulting mixture concentrated. The residue was dissolved in methanol (5 mL) and loaded onto a conditioned SCX cartridge (10 g Varian). The cartridge was washed with methanol (3×20 mL), then eluted with a methanolic ammonia solution (2×15 mL) and the combined elution fractions evaporated. The residue was dissolved in dimethylformamide (5 mL) and triethylamine (0.37 mL) added, followed by di-tert-butyl dicarbonate (0.57 g) and the resulting mixture was stirred for 72 hours. The reaction was concentrated, partitioned between ethyl acetate (50 mL) and saturated aqueous sodium bicarbonate solution (50 mL). The organic phase was separated and the aqueous phase extracted with ethyl acetate (2×50 mL). The combined organics were washed sequentially with water (50 mL), brine (50 mL), dried (magnesium sulfate) and concentrated. Purification on silica, eluting with a gradient of iso-hexane:ethyl acetate [1:0 to 4:1], afforded the subtitle compound as a yellow oil (250 mg).

1. stirringstirred for 18 hours
2. concentrationthe resulting mixture concentrated
3. dissolutionThe residue was dissolved in methanol (5 mL)
4. washThe cartridge was washed with methanol (3×20 mL)
5. washeluted with a methanolic ammonia solution (2×15 mL)
6. washthe combined elution fractions
7. customevaporated
8. dissolutionThe residue was dissolved in dimethylformamide (5 mL)
9. additiontriethylamine (0.37 mL) added
10. stirringthe resulting mixture was stirred for 72 hours
11. concentrationThe reaction was concentrated
12. custompartitioned between ethyl acetate (50 mL) and saturated aqueous sodium bicarbonate solution (50 mL)
13. customThe organic phase was separated
14. extractionthe aqueous phase extracted with ethyl acetate (2×50 mL)
15. washThe combined organics were washed sequentially with water (50 mL), brine (50 mL)
16. dry with materialdried (magnesium sulfate)
17. concentrationconcentrated
18. customPurification on silica
19. washeluting with a gradient of iso-hexane

ORD record

ord-13e37bf4b9534c22aba0b6b522260857

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07951954B2