Dimethyl malonate → 2-[Hydroxy-(2,3,6-trifluoro-phenyl)-methyl]-malonic Acid Dimethyl Ester

HRID 564303Notes

Reaction equation

HRID 564303 reaction equation
[F:1][C:2]1[C:9]([F:10])=[CH:8][CH:7]=[C:6]([F:11])[C:3]=1[CH:4]=[O:5].[C:12]([O:19][CH3:20])(=[O:18])[CH2:13][C:14]([O:16][CH3:17])=[O:15].C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>CN(C=O)C.O>[CH3:17][O:16][C:14](=[O:15])[CH:13]([CH:4]([OH:5])[C:3]1[C:6]([F:11])=[CH:7][CH:8]=[C:9]([F:10])[C:2]=1[F:1])[C:12]([O:19][CH3:20])=[O:18]

Participants

7

Reactant 4

HCID 7943Dimethyl malonateHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 5178452,3,6-Trifluorobenzaldehyde

Product 1

HCID 589506072-[Hydroxy-(2,3,6-trifluoro-phenyl)-methyl]-malonic Acid Dimethyl Ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

2,3,6-trifluorobenzoaldehyde (10.2 g, 63.8 mmol) and dimethyl malonate (8.41 g, 63.8 mmol) were dissolved in 50 mL of DMF. 3 g of K2CO3 was added and the reaction mixture was heated to 80° C. for three hours. 500 mL of EtOAc and 500 mL of water were added. The organic layer washed with saturated NH4Cl solution (200 mL), dried over Na2SO4 and concentrated. The product was purified by column chromatography using EtOAc/hex as the eluent (gradient from 0/100 to 40/60 in 40 min, 13 g, 70%). 1H NMR (CDCl3 400 MHz) δ 7.12 (m, 1H), 6.85 (m, 1H), 5.72 (d, J=9.5 Hz, 1H), 4.17 (d, J=9.5 Hz, 1H), 3.84 (s, 3H), 3.61 (s, 3H).

Workup

  1. washThe organic layer washed with saturated NH4Cl solution (200 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe product was purified by column chromatography
  5. customas the eluent (gradient from 0/100 to 40/60 in 40 min, 13 g, 70%)

Sources & evidence

ORD record
ord-1cf77f74856c4abb95a0ead46fb0972a
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

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