3-(Tert-butyl)isoxazole-5-carboxamide → (3-Tert-butyl-1,2-oxazol-5-yl)methanamine

Temperature

0 °C

To a solution of 220 mg (1.27 mmol) of 3-tert-butyl-isoxazole-5-carboxylic acid amide in anhydrous THF (10 mL) are added 2.54 mL (5.08 mmol, 2M solution in THF) of borane-methylsulfide complex at room temperature under nitrogen atmosphere. The reaction is heated to reflux for 3 h. A further portion of borane-methylsulfide complex (1.3 mL) is added and the reaction is heated for 4 h. The reaction mixture is quenched by addition of methanol and allowed to stand at room temperature for 16 h. The mixture is concentrated under reduced pressure and 1M aqueous HCl solution (8 mL) is added. The mixture is heated to reflux for 1 h, then cooled to 0° C., neutralized by addition of 6M aqueous NaOH solution and solid K2CO3. The mixture is extracted with diethyl ether (5×10 mL) and the combined organic extracts are dried (MgSO4), filtered and the filtrate is concentrated under reduced pressure. The residue is purified twice by column chromatography 9silica, eluent DCM, 0-10% methanol) to afford 84 mg of (3-tert-butyl-1,2-oxazol-5-yl)methanamine. Yield: 34%; ES-MS: m/z 155 [M+H]; 1H NMR (250 MHz, CHLOROFORM-d) δ ppm 1.33 (9 H, s), 1.84 (2 H+H2O, br. s.), 3.96 (2 H, s), 6.07 (1 H, s)

1. temperatureThe reaction is heated
2. temperatureto reflux for 3 h
3. additionA further portion of borane-methylsulfide complex (1.3 mL) is added
4. temperaturethe reaction is heated for 4 h
5. customThe reaction mixture is quenched by addition of methanol
6. concentrationThe mixture is concentrated under reduced pressure and 1M aqueous HCl solution (8 mL)
7. additionis added
8. temperatureThe mixture is heated
9. temperatureto reflux for 1 h
10. additionneutralized by addition of 6M aqueous NaOH solution and solid K2CO3
11. extractionThe mixture is extracted with diethyl ether (5×10 mL)
12. dry with materialthe combined organic extracts are dried (MgSO4)
13. filtrationfiltered
14. concentrationthe filtrate is concentrated under reduced pressure
15. customThe residue is purified twice by column chromatography 9silica, eluent DCM, 0-10% methanol)

ORD record

ord-55313f15b8144df5a3305a4374b046a7

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315454B2