Trifluoroacetic acid → 2-[4-(4-Trifluoromethylbenzyl)piperazin-1-yl]ethanone

HRID 856375ノート

反応式

HRID 856375 の反応式
[N+](C1N=C2N(C=1)CC1(CCN([C:14](=[O:29])[CH2:15][N:16]3[CH2:21][CH2:20][N:19]([C:22](OC(C)(C)C)=O)[CH2:18][CH2:17]3)CC1)O2)([O-])=O.FC(F)(F)C(O)=O.[F:40][C:41]([F:51])([F:50])[C:42]1[CH:49]=[CH:48][C:45](C=O)=[CH:44][CH:43]=1.[B-]C#N.[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl.C(O)(=O)C>[F:40][C:41]([F:51])([F:50])[C:42]1[CH:49]=[CH:48][C:45]([CH2:22][N:19]2[CH2:18][CH2:17][N:16]([CH2:15][CH:14]=[O:29])[CH2:21][CH2:20]2)=[CH:44][CH:43]=1

参加物

8

反応物 5

HCID 6422Trifluoroacetic acidHCID 679964-(Trifluoromethyl)benzaldehydeHCID 516892Sodium BicarbonateHCID 20587905Sodium cyanoborohydride [MI]HCID 69480722Tert-butyl 4-[2-(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazol-2,4'-piperidin]-1'-yl)-2-oxoethyl]piperazine-1-carboxylate

生成物 1

HCID 866048202-[4-(4-Trifluoromethylbenzyl)piperazin-1-yl]ethanone収率 117.8%

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

Tert-butyl 4-[2-(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazole-2,4′-piperidine]-1′-yl)-2-oxoethyl]piperazine-1-carboxylate prepared in Example 653 (300 mg, 0.67 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (10 ml) was added followed by stirring at room temperature for 6 hours. The reaction mixture was concentrated under reduced pressure. To the solution, methylene chloride (1 ml) and triethylamine (1 ml) were added followed by stirring at room temperature for 5 minutes. The solution was concentrated under reduced pressure and the residue was dissolved in methanol (10 ml). To the solution, 4-trifluoromethylbenzaldehyde (0.23 ml, 1.67 mmol), sodium cyanotrihydroborate (105 mg, 1.67 mmol) and acetic acid (0.1 ml) were added with cooling on ice-bath followed by stirring at room temperature overnight. To the solution, a saturated aqueous sodium hydrogencarbonate solution and methylene chloride were added followed by stirring. The organic phase was dried over magnesium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=50/1) and crystallized from methylene chloride-diisopropyl ether to afford 1-(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazole-2,4′-piperidin])-1′-yl)-2-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]ethanone (226 mg, yield 67%) as a white powder.

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionTo the solution, methylene chloride (1 ml) and triethylamine (1 ml) were added
  3. stirringby stirring at room temperature for 5 minutes
  4. concentrationThe solution was concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in methanol (10 ml)
  6. temperaturewith cooling on ice-bath
  7. stirringby stirring at room temperature overnight
  8. stirringby stirring
  9. dry with materialThe organic phase was dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationThe resulting filtrate was concentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=50/1)
  13. customcrystallized from methylene chloride-diisopropyl ether

出典と根拠

ORDレコード
ord-84714c1ef662435c95fba7f383b91500
出典データセット
uspto-grants-2007_08
特許番号
US07262212B2

反応ノート

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