Trifluoroacetic acid → 3,4-Dichlorobenzyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate

HRID 856217

반응식

HRID 856217 반응식
[CH3:1][C:2]1([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29]C(C)(C)C)=[O:28])[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1.FC(F)(F)C(O)=O.[Cl:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][C:49]=1[Cl:50])[CH2:45]O.C(N1C=CN=C1)(N1C=CN=C1)=O>C(Cl)Cl.CN(C=O)C.O>[CH3:1][C:2]1([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:22][CH2:23][N:24]([C:27]([O:29][CH2:45][C:44]4[CH:47]=[CH:48][C:49]([Cl:50])=[C:42]([Cl:41])[CH:43]=4)=[O:28])[CH2:25][CH2:26]3)=[CH:17][CH:16]=2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1

참가 물질

8

반응물 4

HCID 6422Trifluoroacetic acidHCID 157283,4-Dichlorobenzyl alcoholHCID 682631,1'-CarbonyldiimidazoleHCID 23081090Tert-butyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate

생성물 1

HCID 99853183,4-Dichlorobenzyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate수율 70%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

Tert-butyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]-piperazine-1-carboxylate prepared in Example 131 (118 mg, 0.26 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (5 ml) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure and added methylene chloride (2 ml) and triethylamine (2 ml). The solution was stirred at room temperature for 5 minutes and then concentrated under reduced pressure. The residue was dissolved in DMF (15 ml) and the solution was added a solution of 3,4-dichlorobenzyl alcohol (136 mg, 0.77 mmol) and 1,1′-carbonyldiimidazole (125 mg, 0.77 mmol) in DMF (5 ml) stirred at room temperature for 3 hours followed by stirring at room temperature overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with a saturated saline solution, 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=200/1) and crystallized from methylene chloride-isopropyl ether to afford 3,4-dichlorobenzyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate (101 mg, yield 70%) as a light yellow powder.

후처리

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionadded methylene chloride (2 ml) and triethylamine (2 ml)
  3. stirringThe solution was stirred at room temperature for 5 minutes
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in DMF (15 ml)
  6. stirringstirred at room temperature for 3 hours
  7. stirringby stirring at room temperature overnight
  8. extractionextracted with ethyl acetate
  9. washThe organic phase was washed with a saturated saline solution
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationThe resulting filtrate was concentrated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1)
  14. customcrystallized from methylene chloride-isopropyl ether

출처 및 근거

ORD 기록
ord-0552660e0343490c8fa3178e4bad10b5
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07262212B2

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