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

Temperatur

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-Eintrag

ord-3ae47893dddd49129ad88a3c5c6f7428

Quelldatensatz

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08575145B2