Sodium hydride → Methyl 3-[(4-chlorophenyl)carbonyl]-4-oxopentanoate

HRID 563993

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:13])[CH2:9][C:10](=[O:12])[CH3:11])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:17][C:18]([O:20][CH3:21])=[O:19]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([CH:9]([C:10](=[O:12])[CH3:11])[CH2:17][C:18]([O:20][CH3:21])=[O:19])=[O:13])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 20 °C

Procedure

A solution of 10 g (51 mmol) of 1-(4-chlorophenyl)butane-1,3-dione (commercially available) dissolved in dimethyl sulfoxide was slowly added dropwise to 2.237 g (56 mmol) of sodium hydride in 200 ml of dimethyl sulfoxide such that the temperature did not exceed 30° C. The mixture was stirred at 20° C. for another 30 minutes. 8.558 g (56 mmol) of methyl bromoacetate in a little dimethyl sulfoxide were then slowly added dropwise at 0° C. The mixture was stirred at 20° C. for 4 hours. The reaction mixture was poured into ice-water and extracted with dichloromethane. The organic phase was repeatedly washed with water. Drying of the combined organic phases, removal of the solvent under reduced pressure and chromatography of the residue gave 7.750 g of product (56.7% of theory); NMR (CDCl3, 400 MHz): 2.19 (s, 3H); 2.99 (d, 1H); 3.03 (d, 1H); 3.69 (s, 3H); 4.95 (dd, 1H); 7.49 (d, 2H); 7.98 (d, 2H).

Workup

customdid not exceed 30° C
stirringThe mixture was stirred at 20° C. for 4 hours
extractionextracted with dichloromethane
washThe organic phase was repeatedly washed with water
customDrying of the combined organic phases, removal of the solvent under reduced pressure and chromatography of the residue

Sources & evidence

ORD record: ord-6a0aab01bf2c4aba867bb4403f77b4bc
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067611B2

Linked notes

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