Sodium borohydride → Tert-butyl 4-fluoro-5-hydroxyazepane-1-carboxylate

Temperature

0 °C

To a 50 mL flask containing the product from Step B (1.0 g, 4.32 mmol) was added MeOH (20 mL), and the resulting solution was cooled to 0° C. NaBH4 (0.409 g, 10.8 mmol) was carefully added and the mixture stirred at 0° C. for 3.0 hours. The mixture was concentrated to remove the solvent and the residue was taken up in EtOAc (50 mL) and a saturated aqueous NH4Cl solution (20 mL) was added followed by water (20 mL). The layers were mixed and separated and the aqueous phase extracted with EtOAc (2×20 mL). The combined organic extracts were washed with brine and dried over Na2SO4, then filtered and concentrated. The crude product was purified by column chromatography (10% to 60% EtOAc/hexanes gradient) to provide 0.980 g (97%) of the product as a thick colorless oil that solidified to a white solid while standing overnight. The product contained of a mixture of cis and trans isomers.

1. concentrationThe mixture was concentrated
2. customto remove the solvent
3. additiona saturated aqueous NH4Cl solution (20 mL) was added
4. additionThe layers were mixed
5. customseparated
6. extractionthe aqueous phase extracted with EtOAc (2×20 mL)
7. washThe combined organic extracts were washed with brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified by column chromatography (10% to 60% EtOAc/hexanes gradient)

ORD record

ord-2442bf65abdc4d22a7f54c48171398b4

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987251B2