Sodium borohydride → Tert-butyl 3-fluoro-4-hydroxyazepane-1-carboxylate

To a solution of the product from Step B (0.300 g, 1.30 mmol) in MeOH (6 mL) at 0° C. was added NaBH4 (0.123 g, 3.24 mmol) in one portion, and the mixture was warmed to ambient temperature and stirred for 5.0 hours. The mixture was concentrated and the residue was taken up in EtOAc (20 mL) and a saturated aqueous NH4Cl solution (5 mL) and water (5 mL). The layers were mixed and separated and the aqueous phase extracted with EtOAc (2×10 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 (12% to 60% EtOAc/hexanes gradient) to provide 0.130 g (43%) of the major isomer as a colorless oil that solidified overnight to a white solid.

1. concentrationThe mixture was concentrated
2. additionThe layers were mixed
3. customseparated
4. extractionthe aqueous phase extracted with EtOAc (2×10 mL)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified by column chromatography (12% to 60% EtOAc/hexanes gradient)
10. customto provide 0.130 g (43%) of the major isomer as a colorless oil that solidified overnight to a white solid

ORD record

ord-472d4dce232545fa94c4db39addf4849

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575145B2