tert-Butanol → tert-Butyl (5-methylpyrazin-2-yl)carbamate

Temperatur

95 °C

To solution 5-methylpyrazine-2-carboxylic acid (2.5 g, 18.1 mmol), tert-butanol (6.92 mL, 72.4 mmol), Et3N (3.78 mL, 27.1 mmol) in 1,4-dioxane (12.5 mL) at 95° C. was dropwise added diphenylphosphoryl azide (DPPA, 3.23 mL, 18.1 mmol), and the reaction was heated at 95° C. for 1.5 h, followed by a 2nd portion of DPPA (1 mL, 5.6 mmol) and heated for additional 1.5 h. The reaction mixture was cooled down, concentrated and the residue was diluted with EtOAc (50 mL), washed with water (30 mL), 3 M NaOH (30 mL), sat. NaHCO3 (30 mL) and brine (30 mL), dried over Na2SO4, and concentrated. The residue was purified by flashed chromatography on silica gel eluting with gradient EtOAc/CH2Cl2 (0-20%) to afford tert-butyl 5-methylpyrazin-2-ylcarbamate as white solid. LCMS (m/z): 210.1 (MH+), 0.69 min; 1H NMR (400 MHz, CDCl3) δ ppm 9.17 (s, 1H), 8.09 (s, 1H), 7.75 (br. s., 1H), 2.51 (s, 3H), 1.56 (s, 9H).

1. customat 95° C.
2. temperatureheated for additional 1.5 h
3. temperatureThe reaction mixture was cooled down
4. concentrationconcentrated
5. additionthe residue was diluted with EtOAc (50 mL)
6. washwashed with water (30 mL), 3 M NaOH (30 mL), sat. NaHCO3 (30 mL) and brine (30 mL)
7. dry with materialdried over Na2SO4
8. concentrationconcentrated
9. customThe residue was purified

ORD-Eintrag

ord-7f5c9b5bc1f14a22ad2d9dffc64a18f0

Quelldatensatz

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09242996B2