Ethyl Acetoacetate → Ethyl 2-acetyl-4-[3-(4-fluorophenacyl)-1-pyrrolidinyl]butyrate

HRID 1461741Notes

Reaction equation

CS(Cl)(=O)=O.[F:6][C:7]1[CH:23]=[CH:22][C:10]([C:11](=[O:21])[CH2:12][CH:13]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19]O)[CH2:14]2)=[CH:9][CH:8]=1.[C:24]([O:30][CH2:31][CH3:32])(=[O:29])[CH2:25][C:26]([CH3:28])=[O:27].[H-].[Na+]>O1CCCC1.O>[C:26]([CH:25]([CH2:19][CH2:18][N:15]1[CH2:16][CH2:17][CH:13]([CH2:12][C:11]([C:10]2[CH:22]=[CH:23][C:7]([F:6])=[CH:8][CH:9]=2)=[O:21])[CH2:14]1)[C:24]([O:30][CH2:31][CH3:32])=[O:29])(=[O:27])[CH3:28]

Participants

Conditions

Temperature: 15 °C

Procedure

A solution of 3.88 g of methanesulfonyl chloride is added at 0° C. to a suspension of 8.5 g of the product obtained in Stage A in 100 ml of tetrahydrofuran. The mixture is left stirring for 3 hours at 15° C., and this suspension is then added to a solution, cooled to 0° C., of 4.4 g of ethyl acetoacetate containing 1.63 g of sodium hydride in 100 ml of tetrahydrofuran. The mixture is then brought to reflux for 12 hours, hydrolyzed with 5 ml of water and concentrated, and the residue is take up in 150 ml of dichloromethane. The organic phase is washed with 50 ml of water, dried over anhydrous sodium sulfate and concentrated. The oil obtained is purified by chromatography on 600 g of 70-230 mesh silica, using a mixture of dichloromethane and methanol (99:1 V/V) as eluant.

Workup

waitThe mixture is left
additionthis suspension is then added to a solution
concentrationconcentrated
washThe organic phase is washed with 50 ml of water
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated
customThe oil obtained
customis purified by chromatography on 600 g of 70-230 mesh silica
additiona mixture of dichloromethane and methanol (99:1 V/V) as eluant

Sources & evidence

ORD record: ord-9a9c2805151442e494ead4f4dfe2723f
Source dataset: uspto-grants-1991_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05077288

Reaction notes

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