Tert-Butyl isocyanide → 8-Azabicyclo[3.2.1]octane-8-carboxylic acid

A solution (1R,5S)-tert-butyl-3-pent-4-enoyl-8-azabicyclo[3.2.1]-octane-8-carboxylic acid (1.45 g, 4.95 mmol) and ammonium acetate (3.82 g, 49.5 mmol) in 2,2,2-trifluoroethanol (4 mL) was treated with tert-butyl isocyanide (2.06 g, 2.60 mL, 24.75 mmol). After stirring at room temperature for 3 days, the reaction mixture was added to a separatory funnel, diluted with water (20 mL) and extracted with ethyl acetate (2×20 mL). The organic layer was washed with saturated aqueous sodium chloride, dried over MgSO4, filtered and concentrated. Purification by flash column chromatography (silica gel, 10-60% ethyl acetate in heptane) gave (1R,5S)-tert-Butyl-3(2-acetamido)-1-(tert-butylamino)-1-oxo-hex-5-en-2-yl)-8-azabicyclo[3.2.1]octane-8-carboxylic acid as a colorless foam (1.91 g, 89%).; 1H NMR (CDCl3, 400 MHz) δ 6.90 (s, NH, 1H), 5.79 (m, 1H), 5.59 (s, NH, 1H), 4.98 (m, 2H), 4.15 (m, 2H), 2.93 (m, 2H), 2.07 (m, 1H), 2.00 (s, 3H), 1.74-1.96 (m, 3H), 1.50-1.72 (m, 6H), 1.45 (s, 9H), 1.38 (s, 9H), 1.20-1.36 (m, 1H).

1. additionthe reaction mixture was added to a separatory funnel
2. extractionextracted with ethyl acetate (2×20 mL)
3. washThe organic layer was washed with saturated aqueous sodium chloride
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification by flash column chromatography (silica gel, 10-60% ethyl acetate in heptane)

ORD record

ord-f8a6b25349a048e6a248389295fa866c

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266908B2