Acetic Acid → HCID 57791794, compound

Temperature

100 °C

(S)-4-(1-methoxypropan-2-yloxy)pyridine (91) (15 g, 89.71 mmol) and Platinum(IV) oxide in MeOH (50 mL) were stirred under an atmosphere of hydrogen at 50 bar and 80° C. for 16 hours. Analysis indicated no reaction, so 20 ml of acetic acid was added and the temperature increased to 100° C. and pressure increased to 80 bar for another 18 hrs, Still very little reaction observed. An aliquot of 5% Rhodium on alumina was added and the mixture heated overnight at 100° C., 80 bar. GCMS-2 indicated more product formation so reaction put back on at 100° C. again as the impurity peak doesn't seem to be increasing. GCMS-3 indicated more product formation so reaction put back on at 100° C. again for 48 hours as the impurity peak doesn't seem to be increasing. GCMS-4 indicated more product formation so reaction put back on at 100° C. again for 48 hours as the impurity peak doesn't seem to be increasing. GCMS-5 showed just a trace of SM with the main peak being product with the impurity slightly increased. The reaction was filtered and the solvent evaporated, the reaction was quenched with 2M NaOH (75 mL), extracted with EtOAc (3×75 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford a yellow liquid. The crude product was purified by distillation at 0.89 mBar, collecting fractions that distilled at 70° C. to afford the desired compound as a colourless liquid (2.500 g, 16.08% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.14 (3H, d), 1.47-1.37 (2H, m), 1.94-1.83 (2H, m), 2.62-2.56 (2H, m), 3.10-3.06 (2H, m), 3.30-3.26 (1H, m), 3.40-3.36 (4H, m), 3.50-3.44 (1H, m), 3.75-3.66 (1H, m); NH missing.

1. customno reaction
2. temperaturepressure increased to 80 bar for another 18 hrs
3. customStill very little reaction
4. temperaturethe mixture heated overnight at 100° C.
5. customproduct formation so reaction
6. customput back on at 100° C. again as the impurity peak doesn't
7. temperatureto be increasing
8. customproduct formation so reaction
9. temperatureto be increasing
10. customproduct formation so reaction
11. waitput back on at 100° C. again for 48 hours as the impurity peak doesn't
12. temperatureto be increasing
13. temperatureslightly increased
14. filtrationThe reaction was filtered
15. customthe solvent evaporated
16. customthe reaction was quenched with 2M NaOH (75 mL)
17. extractionextracted with EtOAc (3×75 mL)
18. dry with materialthe organic layer was dried over MgSO4
19. filtrationfiltered
20. customevaporated
21. customto afford a yellow liquid
22. distillationThe crude product was purified by distillation at 0.89 mBar
23. customcollecting fractions
24. distillationthat distilled at 70° C.

ORD record

ord-c0b9fe0ebc4a4d879de881654ce4ef0b

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129380B2