Methyl cyanoacetate → Methyl 2-cyano-4-(2-fluorophenyl)-3-methyl-4-oxobutanoate

HRID 1962476Notes

Reaction equation

[C:1]([CH2:3][C:4]([O:6][CH3:7])=[O:5])#[N:2].C(N(C(C)C)CC)(C)C.Br[CH:18]([CH3:28])[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[F:27])=[O:20]>O1CCCC1>[C:1]([CH:3]([CH:18]([CH3:28])[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[F:27])=[O:20])[C:4]([O:6][CH3:7])=[O:5])#[N:2]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of methyl cyanoacetate (15.5 mL) and diisopropylethylamine (64 mL) in tetrahydrofuran (110 mL) was added a solution of 2-bromo-1-(2-fluorophenyl)propan-1-one (36.8 g) in tetrahydrofuran (160 mL), and the mixture was stirred at 70° C. for 20 hr. The reaction mixture was allowed to cool to room temperature, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=5:1) to give the title compound as a brown oil (yield 31.9 g, 80%).

Workup

temperatureto cool to room temperature
filtrationthe insoluble material was filtered off
concentrationthe filtrate was concentrated under reduced pressure
customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=5:1)

Sources & evidence

ORD record: ord-e0ec37f44f2d498d8d8907a733dd8c9b
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415368B2

Reaction notes

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