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

HRID 383746Notes

Reaction equation

HRID 383746 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9](=[O:12])[CH2:10][CH3:11].BrBr.[H-].[Na+].[C:19]([CH2:21][C:22]([O:24][CH3:25])=[O:23])#[N:20].BrC(C)C(C1C=CC=CC=1C(F)(F)F)=O>C(Cl)(Cl)(Cl)Cl.C1COCC1>[CH3:25][O:24][C:22](=[O:23])[CH:21]([C:19]#[N:20])[CH:10]([CH3:11])[C:9](=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[C:2]([F:1])([F:13])[F:14]

Participants

8

Reactant 5

HCID 7747Methyl cyanoacetateHCID 24408BromineHCID 24758Sodium hydrideHCID 1400402-(Trifluoromethyl)propiophenoneHCID 201874742-Bromo-1-[2-(trifluoromethyl)phenyl]propan-1-one

Product 1

HCID 598075352-Cyano-3-methyl-4-oxo-4-(2-trifluoromethyl-phenyl)-butyric acid methyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 2′-trifluoromethyl-propiophenone (10 g, 48 mmol) in carbon tetrachloride (50 ml) was added a solution of bromine (2.72 mL, 52.8 mmol) in carbon tetrachloride (20 mL) dropwise. After the addition was complete, stirring was continued for another 2 h. The solution was washed with satd NaHCO3 and water, dried (anhyd Na2SO4) and concentrated under reduced pressure to give 2-bromo-1-(2-trifluoromethyl-phenyl)-propan-1-one as an oil (12.8 g, 95%), which was used in the next step without purification. 1H-NMR (CDCl3): δ 7.73 (m, 2H), 7.58-7.67 (m, 2H), 4.96 (q, 1H), 1.90 (d, 3H). To a solution of 2′-trifluoromethyl-propiophenone (10 g, 48 mmol) in carbon tetrachloride (50 ml) was added a solution of bromine (2.72 mL, 52.8 mmol) in carbon tetrachloride (20 m 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

  1. customwas used in the next step without purification
  2. stirringthe mixture was stirred overnight at 20° C
  3. customThe mixture was quenched with water
  4. customthe organic layer was separated
  5. extractionThe aqueous layer was extracted with EtOAc
  6. washThe combined extracts were washed with brine
  7. dry with materialdried (anhyd Na2SO4)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a3ee0a4724ff4f4e9d1a18afdf108462
Source dataset
uspto-grants-2013_02
Patent number
US08367667B2

Reaction notes

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