Hydrochloric Acid → (S)-4-(3-(4-Bromophenyl)-3-o-tolylpropanoyl)pyridazin-3(2H)-one

HRID 1527973Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[N:14][C:13]=2[O:18]C)=[O:11])=[CH:4][CH:3]=1.Cl.C(=O)([O-])O.[Na+].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])[CH2:9][C:10]([C:12]2[C:13](=[O:18])[NH:14][N:15]=[CH:16][CH:17]=2)=[O:11])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (S)-3-(4-bromophenyl)-1-(3-methoxypyridazin-4-yl)-3-o-tolylpropan-1-one (example 4, step 1; 312 mg, 759 μmol) in 1,4-dioxane (9 ml) was added 37% aq. hydrochloric acid solution (1.27 ml, 15.2 mmol) and the resulting solution was first stirred at 60° C. for 3 h and then for 2½ h at 80° C. After cooling the reaction mixture was poured onto ice water and ethyl acetate, neutralized with sat. aq. sodium hydrogen carbonate solution and the pH was adjusted to 6.85 with 1 M aq. potassium phosphate buffer solution. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated to afford the title compound (327 mg, quantitative), which was directly used in the next step. Light red foam, MS: 397.1 [M+H]+.

Workup

waitfor 2½ h at 80° C
temperatureAfter cooling the reaction mixture
washThe organic layer was washed with brine
dry with materialdried over magnesium sulfate
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-e88cb08bba59434da709ff9c82be9d36
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090565B2

Reaction notes

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