Water → HCID 59485789, compound

To a solution of (S)-1-(4-(4-chlorophenoxy)phenyl)-5-(3-hydroxyphenyl)-imidazolidin-2-one (26 mg, 0.068 mmol) in acetonitrile (2 mL) is added Cs2CO3 (50 mg, 0.15 mmol) followed by 2-(2-bromoethoxy)tetrahydro-2H-pyran (30 mg, 0.14 mmol). The resulting mixture is stirred at room temperature for 24 h and is then treated with water (5 mL) and extracted with EtOAc (3×3 mL). The combined organic layers are concentrated and the residue is dissolved in MeOH (1 mL). To the MeOH solution is added catalytic amount of pTSA (˜1 mg). The resulting mixture is stirred at room temperature for 1 h and is then treated with sat. NaHCO3 solution (3 mL). After extracting with EtOAc (3×3 mL), the combined organic layers are concentrated and purified by preparative thin layer chromatography (silica gel, 85% EtOAc/hexane) to provide the title compound as a white solid. 1H NMR (CDCl3, 400 MHz) δ 7.33 (d, J=9.2 Hz, 2H), 7.22-7.27 (m, 3H), 6.89 (d, J=7.6 Hz, 1H), 6.81-6.88 (m, 6H), 5.23 (dd, J=8.8, 6.0 Hz, 1H), 4.90 (br s, 1H), 3.92-4.08 (m, 5H), 2.34 (dd, J=8.8, 6.4 Hz, 1H), 2.03 (t, J=5.6 Hz, 1H); HPLC-MS calculated for C23H21ClN2O4 (M+H+) 425.1, found 425.1.

1. extractionextracted with EtOAc (3×3 mL)
2. concentrationThe combined organic layers are concentrated
3. dissolutionthe residue is dissolved in MeOH (1 mL)
4. additionTo the MeOH solution is added catalytic amount of pTSA (˜1 mg)
5. stirringThe resulting mixture is stirred at room temperature for 1 h
6. additionis then treated with sat. NaHCO3 solution (3 mL)
7. extractionAfter extracting with EtOAc (3×3 mL)
8. concentrationthe combined organic layers are concentrated
9. custompurified by preparative thin layer chromatography (silica gel, 85% EtOAc/hexane)

ORD record

ord-77ab1412542443268a05d4e0ce0eddce

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431607B2