4-(Trifluoromethyl)benzaldehyde → 2-Methyl-6-nitro-2-{4-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole

HRID 856218

반응식

HRID 856218 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](OC(C)(C)C)=O)[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.[F:34][C:35]([F:45])([F:44])[C:36]1[CH:43]=[CH:42][C:39](C=O)=[CH:38][CH:37]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>FC(F)(F)C(O)=O.C(Cl)Cl>[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]([CH2:27][C:39]4[CH:42]=[CH:43][C:36]([C:35]([F:45])([F:44])[F:34])=[CH:37][CH:38]=4)[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

참가 물질

7

반응물 4

HCID 679964-(Trifluoromethyl)benzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 23081090Tert-butyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate

생성물 1

HCID 104142242-Methyl-6-nitro-2-{4-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole수율 53.9%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 6422Trifluoroacetic acid용매

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 (88 mg, 0.19 mmol) was dissolved in trifluoroacetic acid (5 ml), and the solution was stirred at room temperature for 5 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 dichloroethane and added 4-trifluoromethylbenzaldehyde (40 μl, 0.29 mmol) and sodium triacetoxyborohydride (82 mg, 0.38 mmol) with cooling on ice-bath followed by stirring at room temperature overnight. To the solution, a saturated sodium hydrogencarbonate solution and methylene chloride were added. The mixture was extracted with methylene chloride, and the organic phase was dried over magnesium sulfate and 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-ethyl acetate to afford 2-methyl-6-nitro-2-{4-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (53 mg, yield 53%) as a white 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 dichloroethane
  6. temperaturewith cooling on ice-bath
  7. stirringby stirring at room temperature overnight
  8. extractionThe mixture was extracted with methylene chloride
  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=200/1)
  13. customcrystallized from methylene chloride-ethyl acetate

출처 및 근거

ORD 기록
ord-225410c9d78c4e5b9e3d6111c11b1fe3
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07262212B2

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