2-Hydrazinoethanol → HCID 67092297, compound

Temperature

75 °C

To a solution of methyl isonicotinate (2 g, 14.58 mmol) in THF (50 mL) was added 4-fluorophenylacetone (2.54 mL, 18.9 mmol) and sodium methoxide powder (1.6 g, 29.17 mmol) was added in one portion with stirring. The resulting suspension was heated to 75° C. for 2 hours under nitrogen, then cooled to ambient and AcOH added (3 mL) followed by EtOH (60 mL) forming a dark orange solution. 2-hydrazinoethanol (3.5 mL, excess) was then added and the mix stirred for 16 hours at room temperature. The volatiles were removed in vacuo and the residue diluted with EtOAc (250 mL) and washed with water (3×50 mL), brine (50 mL), dried over MgSO4, filtered and stripped to a red oil. TLC revealed a mixture of regioisomers that were purified by Biotage flash chromatography, eluting with 2-6% MeOH/DCM, then separated by chiral SF chromatography to afford pure isomers that were characterized by NOE NMR. The title compound was isolated as a white solid, 1.0 g, 23%. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 8.48-8.62 (2 H, m), 7.52-7.65 (2 H, m), 7.14 (2 H, dd, J=8.59, 5.31 Hz), 6.94-7.08 (2 H, m), 6.38 (1 H, s), 4.05-4.14 (2 H, m), 3.94-4.05 (4 H, m), 3.42-3.60 (1 H, m); m/z (APCI+) for C17H16N3FO 297.9 (M+H)+.

1. additionwas added in one portion
2. additionadded (3 mL)
3. customforming a dark orange solution
4. stirringthe mix stirred for 16 hours at room temperature
5. customThe volatiles were removed in vacuo
6. additionthe residue diluted with EtOAc (250 mL)
7. washwashed with water (3×50 mL), brine (50 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. additiona mixture of regioisomers that
11. customwere purified by Biotage flash chromatography
12. washeluting with 2-6% MeOH/DCM
13. customseparated by chiral SF chromatography
14. customto afford pure isomers that

ORD record

ord-d49aa09b8ad2473e90de98219e79f9b7

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07919488B2