Tetrahydrofuran → tert-Butyl 2-isocyanopropionate

Tert-butyl isocyanopropionate was synthesised in two steps from commercially available β-alanine tert-butyl ester hydrochloride (NovaBiochem) as follows. To a solution of β-alanine tert-butyl ester hydrochloride (2 g, 11 mmol) in tetrahydrofuran (5 mL) and ethyl formate (5 mL) was added triethylamine (12 mmol, 1.7 mL). The flask was fitted with a reflux condenser and the mixture was heated for 4 hours, after which another quantity of ethyl formate was added (1 mL). An hour later, the mixture was filtered over silica gel. The silica gel was washed with ethyl acetate. The volatiles were removed from the filtrate, yielding N-formyl β-alanine tert-butyl ester (1.4 g, 11 mmol). 13C-NMR (50 MHz, CDCl3) δ 171.2, 163.4, 80.8, 34.7, 33.4, 22.7; 1H-NMR (200 MHz, CDCl3, TMS) δ 8.15 (s, 1H), 6.31 (broad s, 1H), 3.52 (q, 2H, J=6.1 Hz), 2.47 (t, 2H, J=6.2 Hz), 1.46 (s, 9H). This compound (0.65 g, 3.8 mmol) was subjected to the dehydration conditions described for the above nitrile to afford tert-butyl isocyanopropionate (0.50 g, 3.2 mmol, 85%) as a yellowish liquid. The colour darkened during storage at 4° C. (up to two months), but this did not greatly affect the quality of the product. 1H-NMR (200 MHz, CDCl3, TMS) δ 3.64 (m, 2H), 1.48 (s, 9H).

1. customThe flask was fitted with a reflux condenser
2. temperaturethe mixture was heated for 4 hours
3. filtrationAn hour later, the mixture was filtered over silica gel
4. washThe silica gel was washed with ethyl acetate
5. customThe volatiles were removed from the filtrate

ORD record

ord-229ddc9967694a6681fe091e328f1b96

Source dataset

uspto-grants-2007_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07273951B2