Acetic Acid → 6-(tert-butyl)phthalazin-1(2H)-one

Temperature

90 °C

In a 250 mL round-bottomed flask, 2,5-di-tert-butyl-3-hydroxyisoindolin-1-one (4.9 g, 18.7 mmol, Eq: 1.00) was combined with acetic acid (60 ml) to give a colorless solution. The reaction was heated to 90° C. Hydrazine monohydrate (1.61 g, 1.57 ml, 20.6 mmol, Eq: 1.1) was added dropwise. The reaction was stirred at 90° C. for 1 h. The reaction mixture was diluted with 24 mL H2O and slowly cooled to 25° C. over 3 h. The reaction mixture was concentrated but not quite to dryness. The reaction mixture was taken up in dichloromethane. The reaction mixture was poured into 75 mL sat NaHCO3 and extracted with dichloromethane (3×50 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. to give pure product as a white solid, which was purified by flash chromatography (silica gel, 80 g, 1% to 4% MeOH in DCM) to afford the desired product (3.7 g) as a white solid. (M+H)+=203 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.32 (s, 9 H) 6.58 (d, J=1.89 Hz, 1 H) 6.76 (dd, J=8.31, 1.89 Hz, 1 H) 7.06 (s, 1 H) 7.26 (d, J=8.31 Hz, 1 H) 9.19 (br. s., 1 H).

1. customto give a colorless solution
2. temperatureslowly cooled to 25° C. over 3 h
3. concentrationThe reaction mixture was concentrated but not quite to dryness
4. additionThe reaction mixture was poured into 75 mL
5. extractionextracted with dichloromethane (3×50 mL)
6. dry with materialThe organic layers were dried over Na2SO4
7. concentrationconcentrated in vacuo
8. customto give pure product as a white solid, which
9. customwas purified by flash chromatography (silica gel, 80 g, 1% to 4% MeOH in DCM)

ORD record

ord-232d27a309764daab434b0a9143bb15b

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889682B2