Sodium t-butoxide → (2S,3aR,7aS)-Ethyl 1-((S)-1-phenylethyl)octahydro-1H-indole-2-carboxylate

Temperature

65 °C

Tetrahydrofuran (210 mL) was charged to 1 L flask containing ethyl 2-(((1S,2S)-2-((methylsulfonyloxy)methyl)cyclohexyl)((S)-1-phenylethyl)amino)acetate (14, 30.1 g), sodium t-butoxide (9.6 g) was added at ambient temperature between 19-24° C. under nitrogen. The mixture was then heated to 65° C. and stirred for NLT 1 hour and cooled to 5° C. It was then quenched with a solution of ammonium chloride (10.69 g) in water (34 mL) and concentrated to about 100 mL volume. The mixture was diluted with heptanes (210 mL) and water (105 mL) and the aqueous layer is further extracted with heptanes (2×105 mL). The combined organic layers were washed with water (105 mL), followed by 3.5 M aqueous sodium chloride solution (105 mL). The heptane layer was dried with anhydrous sodium sulfate and concentrated under vacuum to afford 20.65 g of crude compound (15), which was purified on silica gel (700 g) chromatography using 3-4% ethyl acetate in hexanes to afford 8.24 g of (2S,3aR,7aS)-ethyl 1-((S)-1-phenylethyl)octahydro-1H-indole-2-carboxylate (15) as a viscous oil.

1. additionwas added at ambient temperature between 19-24° C. under nitrogen
2. temperaturecooled to 5° C
3. customIt was then quenched with a solution of ammonium chloride (10.69 g) in water (34 mL)
4. concentrationconcentrated to about 100 mL volume
5. additionThe mixture was diluted with heptanes (210 mL) and water (105 mL)
6. extractionthe aqueous layer is further extracted with heptanes (2×105 mL)
7. washThe combined organic layers were washed with water (105 mL)
8. dry with materialThe heptane layer was dried with anhydrous sodium sulfate
9. concentrationconcentrated under vacuum
10. customto afford 20.65 g of crude compound (15), which
11. customwas purified on silica gel (700 g) chromatography

ORD record

ord-7d96ae01319e4d2cbf77cef610fad19f

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288565B2