Tetrabutylammonium Fluoride → (S)-3-methyl-3-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester

Temperature

80 °C

A mixture of (S)-3-methyl-3-[4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.1 g, 2.016 mmol) in a solution of TBAF in THF (1 M, 20 mL, 20 mmoL) was stirred at 80° C. overnight. The reaction mixture was cooled to ambient temperature and diluted with water (25 mL). The aqueous solution was extracted with EtOAc (3×25 mL). The combined organic phase was washed with brine (10 mL), dried over sodium sulfate and filtered. The filtrate was concentrate in vacuo to give the residue, which was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum) to give (S)-3-methyl-3-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.45 g, 54%). 1H NMR (400 MHz, CDCl3) δ 8.19-8.05 (m, 1H), 6.94-6.77 (m, 1H), 6.53-6.23 (m, 2H), 4.74-4.46 (m, 3H), 3.62-3.30 (m, 4H), 2.32-2.17 (m, 1H), 2.00-1.86 (m, 1H), 1.59-1.44 (m, 15H).

1. temperatureThe reaction mixture was cooled to ambient temperature
2. extractionThe aqueous solution was extracted with EtOAc (3×25 mL)
3. washThe combined organic phase was washed with brine (10 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationThe filtrate was concentrate in vacuo
7. customto give the residue, which
8. customwas purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum)

ORD record

ord-c599a7d24ec34ad899cd5cf08994fd37

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115151B2