Sodium hydride → HCID 71515501, compound

Temperature

50 °C

Sodium hydride (60%, 6.00 g, 150 mmol) was taken up in THF (250 mL) under nitrogen atmosphere, and then a solution of 4-fluoro-N′-hydroxybenzimidamide (Step 2; 23.22 g, 150 mmol) in THF (250 mL) was added. The resulting reaction mixture was heated at 50° C. for 15 min, and then a solution of ethyl 2-hydroxy-2-(pyridin-4-yl)propanoate (Step 1; 25 g, 120 mmol) in THF (250 mL) was added. The mixture was stirred for 1 hr at 50° C. The progress of reaction was monitored by TLC using solvent system EtOAc:Hexane (7:3). After completion of reaction, the solvent was concentrated to one third of the total volume. The crude mixture was poured into ice water and extracted with EtOAc (3×500 mL). The combined organic extract was dried over Na2SO4 and concentrated under vacuum. The crude residue was washed with water several times to obtain a solid which was then washed with hexane (100 mL) followed by 50 mL of chilled ether to obtain 14 g (38%) of 1-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)-1-(pyridin-4-yl)ethanol as a colorless solid. HPLC purity: 99.4%; 1H NMR (400 MHz, DMSO-d6): δ 8.58 (d, 2H, J=5.6 Hz), 8.06-8.03 (m, 2H), 7.51 (d, 2H, J=6.4 Hz), 7.39 (t, 2H, J=8.8 Hz), 7.09 (s, 1H), 1.96 (s, 3H); LC-MS m/z calculated for [M+H]+286.09. found 286.1.

1. customThe resulting reaction mixture
2. customThe progress of reaction
3. customAfter completion of reaction
4. concentrationthe solvent was concentrated to one third of the total volume
5. additionThe crude mixture was poured into ice water
6. extractionextracted with EtOAc (3×500 mL)
7. extractionThe combined organic extract
8. dry with materialwas dried over Na2SO4
9. concentrationconcentrated under vacuum
10. washThe crude residue was washed with water several times
11. customto obtain a solid which
12. washwas then washed with hexane (100 mL)

ORD record

ord-85433f2a4a724893a2e39bf02c2c341e

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09371316B2