Trimethyl orthoacetate → 5-Methyl-3-(1-methylpyrazol-3-yl)-1,2,4-oxadiazole

Temperature

90 °C

To a suspension of hydroxylamine hydrochloride (351 mg, 5.05 mmol) in 4 ml EtOH was added 1.86 ml 21% wt sodium ethoxide in ethanol. The resulting mixture was stirred for 10 min at r.t. before addition of 3-cyano-1-methylpyrazole (70) (535 mg, 5 mmol). The resulting suspension was heated overnight at 90° C. After cooling down, the reaction mixture was diluted with EA then washed with brine. Org. phase was concentrated to dryness to give 506 mg crude intermediate 71. A mixture of the above crude intermediate 71, trifluoromethanesulfonic acid Ytterbium (III) salt (22 mg, 1% mol) and trimethyl orthoacetate (550 μl, 1.2 eq.) in 5 ml EtOH was heated at 85° C. for 2 h. After cooling down to r.t., fine needles formed. After filtration and wash with MeOH 166 mg intermediate 71 was recovered as pale yellow needles. The filtrate was concentrated, subjected to silica gel column purification using 0-100% B (A: hexane; B: EA) to furnish 230 mg 5-methyl-3-(1-methylpyrazol-3-yl)-1,2,4-oxadiazole (72) as white solid.

1. additionwas added 1.86 ml 21%
2. temperatureAfter cooling down
3. washthen washed with brine
4. concentrationphase was concentrated to dryness
5. customto give 506 mg crude intermediate 71
6. temperaturewas heated at 85° C. for 2 h
7. temperatureAfter cooling down to r.t.
8. customfine needles formed
9. filtrationAfter filtration
10. washwash with MeOH 166 mg intermediate 71
11. customwas recovered as pale yellow needles
12. concentrationThe filtrate was concentrated
13. customsubjected to silica gel column purification

ORD record

ord-46dc118b2de9427eab97f3f9622ed684

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09120751B2