Water → Diallyl {2-[1-(2-ethoxy-2-oxoethyl)cyclopropyl]ethyl}[4-(methoxycarbonyl)benzyl]malonate

HRID 1920581Notes

Reaction equation

[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[CH:26]=[CH:25][C:10]([CH2:11][CH:12]([C:19]([O:21][CH2:22][CH:23]=[CH2:24])=[O:20])[C:13]([O:15][CH2:16][CH:17]=[CH2:18])=[O:14])=[CH:9][CH:8]=1)=[O:6].Br[CH2:28][CH2:29][C:30]1([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:32][CH2:31]1.O>CN(C=O)C.C(OCC)(=O)C>[CH2:37]([O:36][C:34](=[O:35])[CH2:33][C:30]1([CH2:29][CH2:28][C:12]([CH2:11][C:10]2[CH:9]=[CH:8][C:7]([C:5]([O:4][CH3:3])=[O:6])=[CH:26][CH:25]=2)([C:19]([O:21][CH2:22][CH:23]=[CH2:24])=[O:20])[C:13]([O:15][CH2:16][CH:17]=[CH2:18])=[O:14])[CH2:31][CH2:32]1)[CH3:38]

Participants

Conditions

Temperature: 40 °C

Procedure

Under argon and at 0° C., 1.67 g (41.62 mmol) of sodium hydride (60% strength dispersion in mineral oil) are added a little at a time to a solution of 10.87 g (32.70 mmol) of diallyl [4-(methoxycarbonyl)benzyl]malonate in 60 ml of anhhdrous DMF. The mixture is stirred at 40° C. for 30 min, and a solution of 6.99 g (29.73 mmol) of ethyl [1-(2-bromoethyl)cyclopropyl]acetate in 60 ml of anhydrous DMF is then added dropwise at this temperature. The reaction mixture is subsequently heated at 100° C. for 8 hours. After addition of 600 ml of water and 200 ml of ethyl acetate and phase separation, the aqueous phase is extracted twice with ethyl acetate. The organic phase is then washed five times with water and once with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The crude product is initially purified by flash chromatography (400 g of silica gel 60, mobile phase: cyclohexane/ethyl acetate 4:1), and then by preparative HPLC. This gives 4.87 g (28% of theory) of the title compound in the form of a colorless oil.

Workup

temperatureThe reaction mixture is subsequently heated at 100° C. for 8 hours
extractionthe aqueous phase is extracted twice with ethyl acetate
washThe organic phase is then washed five times with water
dry with materialonce with saturated sodium chloride solution and dried over anhydrous magnesium sulfate
customThe crude product is initially purified by flash chromatography (400 g of silica gel 60, mobile phase: cyclohexane/ethyl acetate 4:1)

Sources & evidence

ORD record: ord-a93f0ab78b574807b78dcc7594c08227
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08168821B2

Reaction notes

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