Dichloromethane → 2-{2-Chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-6-benzyloxypyridine

HRID 1862327Notes

Reaction equation

HRID 1862327 reaction equation
N[C:2]1[C:3]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[N:4][C:5]([O:8][C:9]2[CH:14]=[C:13]([N:15]3[C:20](=[O:21])[CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[N:17]([CH3:26])[C:16]3=[O:27])[C:12]([F:28])=[CH:11][C:10]=2[Cl:29])=[CH:6][CH:7]=1.COCCOC.ClCCl.N(OC(C)(C)C)=O>CCCCC>[Cl:29][C:10]1[CH:11]=[C:12]([F:28])[C:13]([N:15]2[C:20](=[O:21])[CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[N:17]([CH3:26])[C:16]2=[O:27])=[CH:14][C:9]=1[O:8][C:5]1[CH:6]=[CH:7][CH:2]=[C:3]([O:30][CH2:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[N:4]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 80711,2-DimethoxyethaneHCID 10906Tert-Butyl nitriteHCID 186191973-Amino-6-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-benzyloxypyridine

Product 1

HCID 186192252-{2-Chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-6-benzyloxypyridineYield 30.3%

Reagents, catalysts & solvents 1

HCID 8003PentaneSolvent

Procedure

1.38 g of boron trifluoride diethyl ether complex was added to a mixture of 2.55 g of 3-amino-6-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-benzyloxypyridine, 6 ml of 1,2-dimethoxyethane and 2 ml of dichloromethane dropwise at −5° C. The mixture was stirred for 15 minutes at the same temperature, then, to the reaction solution was added 0.59 g of t-butyl nitrite dropwise at −5° C. The mixture was stirred for 1 hour at the same temperature, then, into the mixture was poured n-pentane. The solvent was removed by decantation. 15 ml of ethanol, and 2.3 g of zinc (dust) was added to the residue, and it was stirred at reflux temperature for 1.5 hour. The reaction solution was filtrated through Celite, and the solvent was distilled off, then, the resulted residue was subjected to silica gel chromatography to obtain 0.75 g of 2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-6-benzyloxypyridine.

Workup

  1. stirringThe mixture was stirred for 1 hour at the same temperature
  2. customThe solvent was removed by decantation
  3. addition15 ml of ethanol, and 2.3 g of zinc (dust) was added to the residue, and it
  4. stirringwas stirred
  5. temperatureat reflux temperature for 1.5 hour
  6. filtrationThe reaction solution was filtrated through Celite
  7. distillationthe solvent was distilled off

Sources & evidence

ORD record
ord-146da01086a94ebda538017c3fa2152b
Source dataset
uspto-grants-2003_03
Patent number
US06537948B1

Reaction notes

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