Cesium carbonate → 2-(6-(tert-butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-chlorobenzaldehyde

HRID 2069714

Reaction equation

HRID 2069714 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[NH:10][N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22](F)[C:19]=1[CH:20]=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+].C(O[Si](C)(C)C)C>CN(C=O)C>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:22]1[CH:23]=[CH:24][CH:25]=[C:18]([Cl:17])[C:19]=1[CH:20]=[O:21])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 15772EthoxytrimethylsilaneHCID 678472-Chloro-6-fluorobenzaldehydeHCID 594737656-(tert-Butyl)-8-fluorophthalazin-1(2H)-one

Product 1

HCID 594738282-(6-(tert-butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-chlorobenzaldehydeYield 68.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a 3 L round bottom flask were added 6-tert-butyl-8-fluoro-2H-phthalazin-1-one (132.3 g, 0.6 mol), 2-chloro-6-fluorobenzaldehyde (104.8 g, 0.66 mol) and cesium carbonate (117.4 g, 0.36 mol). The flask was evacuated and backfilled with Nitrogen three times. Then, ethoxytrimethylsilane (142 g, 1.2 mol) and DMF (1.6 L) were added to the reaction flask, and the resulting mixture was heated to 60° C. After 4 h stirring, the solution was allowed to cool down to ambient temperature and the reaction was quenched by addition of 800 mL of H2O dropwise. The desired product started to precipitate from DMF and water mixture. The solid was collected by filtration after cooling down to 5° C., and washed with DMF/water (2/1, 750 mL, pre-cooled to 6° C.) and H2O (400 mL). The filter cake was dried under vacuum oven at 65° C. overnight to afford 147 g of the title compound (68.2% isolated yield) as a yellow solid. MS (ESI) 358, 360 (M+H)−.

Workup

  1. customThe flask was evacuated
  2. temperatureto cool down to ambient temperature
  3. customthe reaction was quenched by addition of 800 mL of H2O dropwise
  4. customto precipitate from DMF and water mixture
  5. filtrationThe solid was collected by filtration
  6. temperatureafter cooling down to 5° C.
  7. washwashed with DMF/water (2/1, 750 mL, pre-cooled to 6° C.) and H2O (400 mL)
  8. customThe filter cake was dried under vacuum oven at 65° C. overnight

Sources & evidence

ORD record
ord-396b71eb90a3446b87114a02d5c1a1a2
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Linked notes

Loading…