Methyl cyanoacetate → 2-Cyano-3-methyl-4-oxo-4-(2-trifluoromethyl-phenyl)-butyric acid methyl ester

HRID 912577Notes

Reaction equation

[H-].[Na+].[C:3]([CH2:5][C:6]([O:8][CH3:9])=[O:7])#[N:4].Br[CH:11]([CH3:24])[C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]([F:23])([F:22])[F:21])=[O:13]>C1COCC1>[CH3:9][O:8][C:6](=[O:7])[CH:5]([C:3]#[N:4])[CH:11]([CH3:24])[C:12](=[O:13])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]([F:21])([F:22])[F:23]

Participants

Conditions

Temperature: 20 °C

Procedure

To a suspension of NaH (60%, 2.88 g, 72 mmol) in anhyd THF (200 mL) was added methyl cyanoacetate (4.5 mL, 50 mmol). After this mixture was stirred for 3 h at 20° C., a solution of 2-bromo-1-(2-trifluoromethyl-phenyl)-propan-1-one (13.5 g, 48 mmol) was added and the mixture was stirred overnight at 20° C. The mixture was quenched with water and the organic layer was separated. The aqueous layer was extracted with EtOAc. The combined extracts were washed with brine, dried (anhyd Na2SO4) and concentrated under reduced pressure to afford the title compound as an oil (13.3 g, 93%), which was used in the next step without purification. MS (ES): 300 (MH+).

Workup

stirringthe mixture was stirred overnight at 20° C
customThe mixture was quenched with water
customthe organic layer was separated
extractionThe aqueous layer was extracted with EtOAc
washThe combined extracts were washed with brine
dry with materialdried (anhyd Na2SO4)
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-a3a00388fd38447484558a00fb642afc
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026237B2

Reaction notes

Loading…