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

HRID 1972247Notes

Reaction equation

[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[N:8]=[CH:9][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([OH:24])[CH:19]=4)[CH2:16][CH2:15][C:14]3=[O:25])=[N:11][CH:12]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].I[CH2:35][CH2:36][OH:37]>CC(C)=O>[OH:37][CH2:36][CH2:35][O:24][C:20]1[CH:19]=[C:18]([C@@H:17]2[N:13]([C:10]3[CH:9]=[N:8][C:7]([O:6][C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:27][CH:26]=4)=[CH:12][N:11]=3)[C:14](=[O:25])[CH2:15][CH2:16]2)[CH:23]=[CH:22][CH:21]=1

Participants

Conditions

Temperature: 70 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-0db7d6bc3c9040f2a4c4e737194e0577
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431607B2

Reaction notes

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