Ethyl Acetate → 4-[3-(4-Chlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde

HRID 403563Notes

Reaction equation

HRID 403563 reaction equation
[F:1][CH:2]([F:25])[CH2:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH:15]1[CH2:20][CH2:19][N:18]([CH:21]=[O:22])[CH2:17][CH2:16]1)[C:10](=[O:23])[NH:9][C:8]2=[O:24].Br[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1.C([O-])([O-])=O.[Cs+].[Cs+].CCOC(C)=O>CN(C=O)C>[Cl:34][C:31]1[CH:32]=[CH:33][C:28]([CH2:27][N:9]2[C:8](=[O:24])[C:7]3[C:12](=[CH:13][CH:14]=[C:5]([O:4][CH2:3][CH:2]([F:1])[F:25])[CH:6]=3)[N:11]([CH:15]3[CH2:20][CH2:19][N:18]([CH:21]=[O:22])[CH2:17][CH2:16]3)[C:10]2=[O:23])=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 252533494-[6-(2,2-Difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde

Product 1

HCID 252535004-[3-(4-Chlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehydeYield 57.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 0.15 g of 4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde obtained in stage 3.7, 0.096 g of 1-(bromomethyl)-4-chlorobenzene and 0.3 g of Cs2CO3 in 3 ml of DMF is stirred at AT for 1 h 00. AcOEt is added and washing is carried out with water and then with a saturated NaCl solution. The organic phase is dried over MgSO4, filtered and evaporated under reduced pressure. The residue is chromatographed on silica gel, elution being carried out with AcOEt, to give 0.116 g of the expected product.

Workup

  1. washwashing
  2. dry with materialThe organic phase is dried over MgSO4
  3. filtrationfiltered
  4. customevaporated under reduced pressure
  5. customThe residue is chromatographed on silica gel, elution

Sources & evidence

ORD record
ord-60f9f1bcd7424e3fb6c80d377cf24f66
Source dataset
uspto-grants-2014_06
Patent number
US08748441B2

Reaction notes

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