Water → HCID 45789195, compound

Temperature

80 °C

Ethyl (1R,2R)-1-(tert-butoxycarbonylamino)-2-vinyl-cyclopropane-1-carboxylate (2.0 g, 7.84 mmol., 1.0 eq.), water (60 mL) and tetrahydrofuran (50 mL) were charged into a 250 mL round bottom flask placed in ice/water bath. Lithium hydroxide monohydrate (0.523 g, 12.94 mmol., 1.65 eq.) was added portion wise and the reaction mixture heated at 80° C. for 15 hours. TLC analysis of the reaction mixture (heptanes:ethyl acetate, 1:1) showed full consumption of the starting material. The reaction mixture was left to cool down to ambient temperature and diluted with ethyl acetate (50 mL). The organic phase was discarded, and the aqueous phase washed further with ethyl acetate (50 mL). The aqueous phase was acidified to pH 3 by slow addition of 1M hydrochloric acid then extracted with ethyl acetate (2×80 mL). The organic extracts were pooled, washed with brine (50 mL), dried over sodium sulphate, filtered and concentrated to dryness to give 1.72 g (96%) of the title compound as a pale yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 5.67-5.86 (m, 1 H), 5.31 (d, J=17.10 Hz, 1 H), 5.18-5.28 (m, 1 H), 5.15 (d, J=10.32 Hz, 1 H), 2.20 (q, J=8.86 Hz, 1 H), 1.70-1.92 (m, 1 H), 1.50-1.65 (m, 1 H), 1.46 (s, 9 H). LC-MS: purity 100% (ELS), tR 1.56 min, m/z [M−H]-226.10.

1. customconsumption of the starting material
2. waitThe reaction mixture was left
3. temperatureto cool down to ambient temperature
4. additiondiluted with ethyl acetate (50 mL)
5. washthe aqueous phase washed further with ethyl acetate (50 mL)
6. additionThe aqueous phase was acidified to pH 3 by slow addition of 1M hydrochloric acid
7. extractionthen extracted with ethyl acetate (2×80 mL)
8. washwashed with brine (50 mL)
9. dry with materialdried over sodium sulphate
10. filtrationfiltered
11. concentrationconcentrated to dryness

ORD record

ord-f7fce1145974450bae4620c6fd9e6a6d

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08048862B2