Tetrahydrofuran → HCID 60108792, compound

Temperature

-5 °C

A solution of 7-bromoindole (1.25 g, 6.4 mmol) in THF (15 mL) under Argon was cooled to −70° C., and n-BuLi (9.6 mL, 19.2 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 (2.5 g, 12.8 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 water (10 mL) and partitioned between water (25 mL) and ethyl acetate (50 mL). The organic layer was washed with water (15 mL) and brine (30 mL), then dried (MgSO4), filtered and concentrated. The remaining brown oil was chromatographed, eluting with acetone:hexanes (1:4) to afford 1.17 g (58% yield) of 4-hydroxy-4-(1-H-indol-7-yl)-piperidine-1-carboxylic acid tert-butyl ester XVI.

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 water (10 mL)
5. custompartitioned between water (25 mL) and ethyl acetate (50 mL)
6. washThe organic layer was washed with water (15 mL) and brine (30 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe remaining brown oil was chromatographed
11. washeluting with acetone:hexanes (1:4)

ORD record

ord-fae095014bab4547a0b7d92d5e379202

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07247651B2