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

HRID 1047482

Reaction equation

HRID 1047482 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 was 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 was 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-72bbc11ee2ba4d6e9ead3221ace42dd6
Source dataset
uspto-grants-2013_10
Patent number
US08569521B2

Linked notes

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