Hydrochloric Acid → 1-tert-Butyl-1H-pyrazole

To a mixture of 1,1,3,3-tetramethoxypropane (3.82 kg, 23.27 mol) and tert-butylhydrazine hydrochloride (2.9 kg, 23.27 mol) in ethanol (24.54 kg), conc HCl (4.72 kg, 46.55 mol) was added, keeping the temperature below 50° C. The reaction mixture was then rapidly heated to reflux. After ca. 2 h the reaction was sampled and analysed by NMR. Pass criteria was <3.0% starting material remaining. On receipt of a pass result the solution is cooled, diluted with water (8.29 kg) and evaporated in vacuo (T<50° C., p<−0.08 MPa) until approximately all of the original ethanol was removed. The solution was basified with 10M NaOH(aq), extracted with EtOAc (11.11 kg×2) and the organic phase washed with saturated ammonium chloride solution (4.3 ml/g×2) and brine (4.3 ml/g), then evaporated to give the title compound (2.08 kg, 72% yield) as a brown liquid (GC purity 99.70% a/a).

1. additionwas added
2. customthe temperature below 50° C
3. temperatureThe reaction mixture was then rapidly heated to reflux
4. aliquotAfter ca. 2 h the reaction was sampled
5. customOn receipt of a pass result the solution
6. temperatureis cooled
7. customevaporated in vacuo (T<50° C., p<−0.08 MPa) until approximately all of the original ethanol
8. customwas removed
9. extractionextracted with EtOAc (11.11 kg×2)
10. washthe organic phase washed with saturated ammonium chloride solution (4.3 ml/g×2) and brine (4.3 ml/g)
11. customevaporated

ORD-Eintrag

ord-55aedbb7da2f4542ae3adf48608a028d

Quelldatensatz

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08633319B2