Water → benzyl 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylcarbamate

HRID 62049

반응식

HRID 62049 반응식
P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:10]1[N:14]=[CH:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[N:11]=1.CC1(C)C(C)(C)OB([C:34]2[CH:51]=[CH:50][C:37]([CH2:38][NH:39][C:40](=[O:49])[O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[CH:36][CH:35]=2)O1.O>O1CCOCC1.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.Cl[Pd]Cl.[Fe]>[F:23][C:22]([F:25])([F:24])[O:21][C:18]1[CH:19]=[CH:20][C:15]([N:12]2[CH:13]=[N:14][C:10]([C:34]3[CH:51]=[CH:50][C:37]([CH2:38][NH:39][C:40](=[O:49])[O:41][CH2:42][C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)=[CH:36][CH:35]=3)=[N:11]2)=[CH:16][CH:17]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 712094283-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazoleHCID 90404705benzyl N-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}carbamate

생성물 1

HCID 90404490benzyl 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylcarbamate수율 87%

시약·촉매·용매 2

HCID 178454869HCID 178454869, 화합물촉매HCID 312751,4-Dioxane용매

반응 조건

온도
75 °C

실험 절차

To a 5.0 mL vial, [1,1′-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (0.011 mg, 0.017 mmol), and potassium phosphate (0.14 g, 0.65 mmol) were charged as solids. The vial was sealed with a septum and placed under nitrogen. A solution of 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (WO 2013/009791) (0.10 g, 0.33 mmol) and benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (0.13 g, 0.36 mmol) in dioxane (1.8 mL) was added followed by water (0.45 mL). The reaction mixture was evacuated with vacuum and purged with nitrogen and placed in a pre-heated heating block that at 75° C. for 18 hours. The reaction mixture was then poured into brine solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated. The resulting residue was purified via flash chromatography using 15-80% ethyl acetate/hexanes as eluent to afford the title compound as a white solid (0.13 g, 87%): 1H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 8.16-8.01 (m, 4H), 7.91 (t, J=6.2 Hz, 1H), 7.67-7.58 (m, 2H), 7.48-7.15 (m, 7H), 5.07 (s, 2H), 4.28 (d, J=6.2 Hz, 2H); 19F NMR (376 MHz, DMSO-d6) δ −56.96; ESIMS m/z 469 ([M+H]+).

후처리

  1. customThe vial was sealed with a septum
  2. customThe reaction mixture was evacuated with vacuum
  3. custompurged with nitrogen
  4. additionThe reaction mixture was then poured into brine solution
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified via flash chromatography

출처 및 근거

ORD 기록
ord-a3f121d2ec7649d7a28443ba9082df68
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09445594B2

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