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

Temperatur

82 °C

To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added 5-methylpyrazine-2-carboxylic acid (1.0 eq), tert-butanol (3.5 vols) and di-isopropylethylamine (1.5 eq) under a nitrogen atmosphere. The mixture was heated to 82° C., then diphenylphosphorylazide (1.0 eq) was added over a time period of 5-14 hours, maintaining the temperature of the reaction mixture at approximately 82° C. The reaction mixture was stirred for at least 1.5 hours, and then cooled to approximately 60° C. A solution of 4% w/w sodium hydroxide (1.75 eq) was added over a period of 2 hours. The mixture was cooled to 15° C. over at least 5 hours then held at 15° C. for 3 hours. The batch was then filtered, and the solid slurry washed with water (2 vols). The batch was again slurry washed with water (2 vols). After drying at 55-60° C. overnight, the desired product was obtained as a solid (corrected yield 56-63%). 1H NMR δ (400 MHz CDCl3): 9.18 (s, 1H), 8.17 (bs, 1H), 8.11 (s, 1H), 2.51 (s, 3H), 1.56 (s, 9H)

1. customTo a flask fitted with overhead stirrer, condenser
2. temperaturemaintaining the temperature of the reaction mixture at approximately 82° C
3. temperaturecooled to approximately 60° C
4. temperatureThe mixture was cooled to 15° C. over at least 5 hours
5. filtrationThe batch was then filtered
6. washthe solid slurry washed with water (2 vols)
7. washThe batch was again slurry washed with water (2 vols)
8. customAfter drying at 55-60° C. overnight

ORD-Eintrag

ord-6bf32cd39e804629add260e00c22016d

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08093252B2