1-Chloro-4-(chloromethyl)benzene → 4-(4-Chlorobenzyloxy)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one

HRID 1044404Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]Cl)=[CH:4][CH:3]=1.[OH:10][C:11]1[CH:16]=[CH:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([OH:28])([CH3:27])[CH3:26])=[C:19]([O:29][CH3:30])[CH:18]=2)[C:13](=[O:31])[CH:12]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:10][C:11]2[CH:16]=[CH:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([OH:28])([CH3:26])[CH3:27])=[C:19]([O:29][CH3:30])[CH:18]=3)[C:13](=[O:31])[CH:12]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 1-chloro-4-(chloromethyl)benzene (26.4 mg, 0.16 mmol), 4-hydroxy-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one Part C (50 mg, 0.16 mmol) and K2CO3 (67.9 mg, 0.49 mmol) in DMF (1.0 mL) was stirred at 100° C. for 90 min The mixture was cooled to RT, filtered and the filtrate was concentrated. The crude product was purified by prep-HPLC (C18 column/Water:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient) yielding the title compound D-2-4-(4-chlorobenzyloxy)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one D-2 (30 mg, 41.2% yield) as white solid. LC/MS 430 (M+H)+, tR 0.93 min (method 5); 1H NMR (400 MHz, Chloroform-D) δ ppm 7.32-7.44 (4H, m), 7.24-7.28 (1H, m), 6.96 (1H, d, J=8.53 Hz), 6.80-6.91 (2H, m), 6.06-6.18 (2H, m), 5.03 (2H, s), 3.85 (5H, d, J=1.76 Hz), 1.35 (6H, s).

Workup

temperaturewas cooled to RT
filtrationfiltered
concentrationthe filtrate was concentrated
customThe crude product was purified by prep-HPLC (C18 column/Water:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient)

Sources & evidence

ORD record: ord-d99abab05ad04fd593fb4970b44520e8
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08563583B2

Reaction notes

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