Potassium Carbonate → (R)-5-[3-(2-hydroxyethoxy)phenyl]-1-[5-(4-chlorophenoxy)pyrazin-2-yl]pyrrolidin-2-one

Temperature

70 °C

A mixture of (R)-1-[5-(4-chlorophenoxy)pyrazin-2-yl]-5-(3-hydroxyphenyl)pyrrolidin-2-one (276 mg, 0.72 mmol), acetone (9 mL), K2CO3 (996 mg, 7.2 mmol) and 2-iodoethanol (1.86 g, 10.8 mmol) is stirred at 70° C. for 65 h. Then, acetone is removed by evaporation and the residue is dissolved in ethyl acetate (120 mL), washed with brine (20 mL) and dried over Na2SO4. After concentration, the residue is purified on silica gel (0-50% ethyl acetate in hexane) to give the title compound (215 mg, 70%) as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 9.12 (s, 1H), 7.99 (s, 1H), 7.37-7.32 (m, 2H), 7.22 (t, J=7.6 Hz, 1H), 7.08-7.03 (m, 2H), 6.84-6.74 (m, 3H), 5.68 (dd, J=8.0, 3.2 Hz, 1H), 4.09-3.99 (m, 2H), 3.98-3.92 (m, 2H), 2.89-2.75 (m, 1H), 2.72-2.58 (m, 2H), 2.09-1.98 (m, 1H). HPLC-MS calculated for C22H20ClN3O4 (M+H+) 426.12, found 426.10.

1. customThen, acetone is removed by evaporation
2. dissolutionthe residue is dissolved in ethyl acetate (120 mL)
3. washwashed with brine (20 mL)
4. dry with materialdried over Na2SO4
5. concentrationAfter concentration
6. customthe residue is purified on silica gel (0-50% ethyl acetate in hexane)

ORD record

ord-0db7d6bc3c9040f2a4c4e737194e0577

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431607B2