Hydrochloric Acid → 1154569-98-8

To a mixture of acetonitrile (0.50 mL, 9.57 mmol) in THF (30 ml) at RT was added potassium 2-methylbutan-2-olate (1.7M solution in 2-methyl-butan-2-ol, 16.9 mL, 28.7 mmol). On completion of the addition ethyl isobutyrate (5.12 mL, 38.3 mmol) was added dropwise and the mixture was maintained at RT for 16 hr. The reaction mixture was concentrated in vacuo to ca 20 mL, was diluted with ethanol (20 mL) and p-tolylhydrazine hydrochloride (1.52 g, 9.57 mmol) was added. The resulting mixture was acidified to pH1 by the addition of conc. hydrochloric acid and the mixture was then heated to 70° C. for 2 hr. The mixture was cooled to RT and was concentrated in vacuo to ca 20 mL and then diluted with water (30 mL). The aq. mixture was adjusted to pH12 by the addition of aq NaOH solution (6M) and was then extracted with EtOAc (2×20 mL). The combined organic extracts were washed with brine (30 mL) and then dried (MgSO4) and evaporated in vacuo to afford the title compound as a brown oil (1.78 g, 90% pure, 72%); Rt 1.32 min (Method 2); m/z 216 (M+H)+ (ES+). This material was used directly in the next step, without further purification.

1. additionwas added dropwise
2. concentrationThe reaction mixture was concentrated in vacuo to ca 20 mL
3. additionwas added
4. temperaturethe mixture was then heated to 70° C. for 2 hr
5. temperatureThe mixture was cooled to RT
6. concentrationwas concentrated in vacuo to ca 20 mL
7. additiondiluted with water (30 mL)
8. additionThe aq. mixture was adjusted to pH12 by the addition of aq NaOH solution (6M)
9. extractionwas then extracted with EtOAc (2×20 mL)
10. washThe combined organic extracts were washed with brine (30 mL)
11. dry with materialdried (MgSO4)
12. customevaporated in vacuo

ORD record

ord-dcb9b07a2d5a4dff9fa39e08563b22ab

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299074B2