Dimethylformamide dimethyl acetal → Methyl 2-(4-cyano-5-fluoro-2-methylphenyl)-3-(dimethylamino)acrylate

HRID 526454Notes

Reaction equation

HRID 526454 reaction equation
[C:1]([C:3]1[C:8]([F:9])=[CH:7][C:6]([CH2:10][C:11]([O:13][CH3:14])=[O:12])=[C:5]([CH3:15])[CH:4]=1)#[N:2].CO[CH:18](OC)[N:19]([CH3:21])[CH3:20].[Cl-].[Li+]>CCOC(C)=O>[C:1]([C:3]1[C:8]([F:9])=[CH:7][C:6]([C:10](=[CH:18][N:19]([CH3:21])[CH3:20])[C:11]([O:13][CH3:14])=[O:12])=[C:5]([CH3:15])[CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 78373Dimethylformamide dimethyl acetalHCID 433294Lithium ChlorideHCID 117600964HCID 117600964, compound

Product 1

HCID 117601464Methyl 2-(4-cyano-5-fluoro-2-methylphenyl)-3-(dimethylamino)acrylateYield 96.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Combined methyl 2-(4-cyano-5-fluoro-2-methylphenyl)acetate (5.00 g, 24.13 mmol), 1,1-dimethoxy-N,N-dimethylmethanamine (32.2 mL, 241 mmol), and lithium chloride (0.102 g, 2.413 mmol) and heated to 105° C. After 2 hours the reaction mixture was concentrated in vacuo and repeatedly diluted with EtOAc (30 mL) and concentrated to give an oil. The oil was dissolved in EtOAc (50 mL) and washed with water, 10% aqueous sodium chloride, and then brine. The organic layer was dried over sodium sulfate, filtered, and concentrated to afford a thick red oil, which was crystallized to give the title compound as a yellow solid (6.1 g, 23.26 mmol, 96%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.10 (s, 3H) 2.34 (s, 1H) 2.54-2.81 (m, 6H) 3.50 (s, 3H) 7.20 (d, J=10.11 Hz, 1H) 7.58 (s, 1H) 7.72 (d, J=7.07 Hz, 1H). ESI-MS m/z [M+H]+ 263.2.

Workup

  1. concentrationAfter 2 hours the reaction mixture was concentrated in vacuo
  2. additionrepeatedly diluted with EtOAc (30 mL)
  3. concentrationconcentrated
  4. customto give an oil
  5. washwashed with water, 10% aqueous sodium chloride
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford a thick red oil, which
  10. customwas crystallized

Sources & evidence

ORD record
ord-9d3c68bd67f9426ba1b2141029eff784
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Reaction notes

Loading…