Hydrochloric Acid → Methyl 4-(3-chlorophenyl)-5-(5-chloropyridin-2-yl)-5-oxopentanoate

HRID 932046Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][N:12]=2)=[O:10])[CH:5]=[CH:6][CH:7]=1.C1CCN2C(=NCCC2)CC1.[C:29]([O:33][CH3:34])(=[O:32])[CH:30]=[CH2:31].Cl.C([O-])(O)=O.[Na+]>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][N:12]=2)=[O:10])[CH2:31][CH2:30][C:29]([O:33][CH3:34])=[O:32])[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 368.5 g (1.39 mol) of 2-(3-chlorophenyl)-1-(5-chloropyridin-2-yl)ethanone (Example 121, Step B) in dioxane (1.5 L) at 80° C. was added DBU (207 mL, 1.39 mole, 1 eq), followed by dropwise addition of methyl acrylate (124.7 mL, 1.39 mol, 1 eq) at 80° C. The reaction was stirred at 80° C. for 1 h 30 min and then allowed to cool to ambient temperature. It was quenched with 2 M aqueous HCl solution (56.5 eq) and then basified to pH 7 with saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc (2×4 L). The combined organic layers were dried over Na2SO4, filtered and the filtrate was evaporated. Purification by flash chromatography on silica gel (eluent: 40 to 100% DCM/hexanes) provided the title compound as a yellow liquid.

Workup

temperatureto cool to ambient temperature
extractionThe aqueous layer was extracted with EtOAc (2×4 L)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
customthe filtrate was evaporated
customPurification by flash chromatography on silica gel (eluent: 40 to 100% DCM/hexanes)

Sources & evidence

ORD record: ord-7a88fd795bab4b20bd666fbe4e75a877
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296736B2

Reaction notes

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