Tetrahydrofuran → 4-(1-Tert-butoxycarbonyl-4-hydroxy-piperidin-4-yl)-indole-1-carboxylic acid tert-butyl ester

Temperature

-5 °C

A solution of 4-bromo-indole-1-carboxylic acid-tert-butyl ester 4-2 (4.9 g, 16.5 mmol) in THF (150 mL) under Argon was cooled to −70° C., and n-BuLi (12.4 mL, 24.8 mmol) was added over 20 min. The reaction mixture was warmed to −5° C. in an ice bath and was stirred at this temperature for 30 min. The mixture was cooled to −70° C. and a solution of N-Boc-piperidone 4-3 (3.3 g, 16.5 mmol) in THF (10 mL) was added over 15 min. The reaction was stirred for 45 min at −70° C. and was then warmed to room temperature. The reaction was quenched with a saturated solution of ammonium chloride (75 mL) and partitioned between water (25 mL) and ethyl acetate (75 mL). The organic layer was washed with water (50 mL) and brine (50 mL), then dried (MgSO4), filtered and concentrated. The remaining brown oil was chromatographed, eluting with ethyl acetate:hexanes (1:9) to afford 1.32 g (19% yield) of 4-(1-tert-butoxycarbonyl-4-hydroxy-piperidin-4-yl)-indole-1-carboxylic acid tert-butyl ester 4-4.

1. temperatureThe mixture was cooled to −70° C.
2. stirringThe reaction was stirred for 45 min at −70° C.
3. temperaturewas then warmed to room temperature
4. customThe reaction was quenched with a saturated solution of ammonium chloride (75 mL)
5. custompartitioned between water (25 mL) and ethyl acetate (75 mL)
6. washThe organic layer was washed with water (50 mL) and brine (50 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe remaining brown oil was chromatographed
11. washeluting with ethyl acetate:hexanes (1:9)

ORD record

ord-11baaf0a693449f8a3b0c963c6a0f912

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07381739B2