Ethyl Acetate → phosphoric acid di-tert-butyl ester 4-{4-[(2,6-dichloro-benzoylamino)-methyl]-phenyl}-2-oxo-2H-pyridin-1-ylmethyl ester

HRID 2038350Notes

Reaction equation

HRID 2038350 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][N:17]([CH2:20]Cl)[C:16](=[O:22])[CH:15]=2)=[CH:10][CH:9]=1)=[O:5].C(=O)([O-])[O-].[K+].[K+].[C:34]([O:38][P:39]([O-:46])([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])([CH3:37])([CH3:36])[CH3:35].[K+].C(OCC)(=O)C>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][N:17]([CH2:20][O:46][P:39](=[O:40])([O:38][C:34]([CH3:37])([CH3:36])[CH3:35])[O:41][C:42]([CH3:43])([CH3:44])[CH3:45])[C:16](=[O:22])[CH:15]=2)=[CH:10][CH:9]=1)=[O:5]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 23674467Potassium di-tert-butyl phosphateHCID 866754212,6-dichloro-N-[4-(1-chloromethyl-2-oxo-1,2-dihydro-pyridin-4-yl)-benzyl]-benzamide

Product 1

HCID 71149943phosphoric acid di-tert-butyl ester 4-{4-[(2,6-dichloro-benzoylamino)-methyl]-phenyl}-2-oxo-2H-pyridin-1-ylmethyl ester

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

2,6-Dichloro-N-[4-(1-chloromethyl-2-oxo-1,2-dihydro-pyridin-4-yl)-benzyl]-benzamide from the previous step was dissolved in 50 mL DMF. Potassium carbonate (1 g) was added followed by potassium di(t-butyl)phosphate (2 g) and tetrabutylammonium iodide (50 mg). The mixture was stirred at 70° C. for four hours after which it was poured into 300 mL ethyl acetate. The organic phase was washed with water and brine, dried with magnesium sulfate and evaporated under vacuum. The crude product was further purified by silica gel chromatography (eluent: ethyl acetate), giving phosphoric acid di-tert-butyl ester 4-{4-[(2,6-dichloro-benzoylamino)-methyl]-phenyl}-2-oxo-2H-pyridin-1-ylmethyl ester as a colorless oil which slowly crystallized.

Workup

  1. washThe organic phase was washed with water and brine
  2. dry with materialdried with magnesium sulfate
  3. customevaporated under vacuum
  4. customThe crude product was further purified by silica gel chromatography (eluent: ethyl acetate)

Sources & evidence

ORD record
ord-f7441242dcfd430aa7d36c45d3afe44e
Source dataset
uspto-grants-2013_11
Patent number
US08575353B2

Reaction notes

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