Nitrogen → 5-(2,2-Difluorocyclopropoxy)-2-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridine

HRID 63260

반응식

HRID 63260 반응식
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([C:12]([F:23])([F:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH:20]=[CH2:21])=[CH:15][N:14]=2)CO1.C[Si](C)(C)[C:26](F)([F:28])[F:27].[I-].[Na+].N#N.[C:36]([O-:39])(O)=O.[Na+]>C1COCC1.[Cl-].[Na+].O>[F:27][C:26]1([F:28])[CH2:21][CH:20]1[O:19][C:16]1[CH:17]=[CH:18][C:13]([C:12]([C:9]2([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[CH2:36][O:39]2)([F:22])[F:23])=[N:14][CH:15]=1

참가 물질

8

반응물 5

HCID 947NitrogenHCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 552549(Trifluoromethyl)trimethylsilaneHCID 893090892-((2-(2,4-Difluorophenyl)oxiran-2-yl)difluoromethyl)-5-(vinyloxy)pyridine

생성물 1

HCID 1177203945-(2,2-Difluorocyclopropoxy)-2-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridine수율 82%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
110 °C

실험 절차

To a magnetically stirred mixture of 2-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)-5-(vinyloxy)pyridine (227 mg, 0.698 mmol) (prepared as in WO 2012/177635 A1) and trimethyl(trifluoromethyl)silane (1546 μL, 10.47 mmol) in dry THF (3034 μl) was added sodium iodide (84 mg, 0.558 mmol) in a 10 mL microwave vial under N2 atmosphere. The reaction mixture was stirred at 110° C. for 1 h 20 min Upon completion of the reaction in the microwave, the reaction was poured into a 1:1 mixture of brine and sat. aq. NaHCO3 and extracted with EtOAc (3×). The combined organic layers were dried by passing through a phase separator and volatiles were removed under a gentle stream of N2. The brown oil was loaded onto a pad of Celite® and purified by flash chromatography (SiO2, 5-25% EtOAc/Hexanes over 6 min, 25% for 4 min) to yield the title compound as a brown oil (215 mg, 82%): 1H NMR (400 MHz, CDCl3) δ 8.43 (d, J=2.8 Hz, 1H), 7.46 (d, J=8.7 Hz, 1H), 7.42-7.32 (m, 2H), 6.87-6.81 (m, 1H), 6.78-6.71 (m, 1H), 4.19-4.10 (m, 1H), 3.43 (t, J=4.8 Hz, 1H), 3.00-2.94 (m, 1H), 1.91 (dddd, J=14.4, 9.7, 8.8, 6.5 Hz, 1H), 1.71 (ddd, J=20.2, 9.8, 4.9 Hz, 1H); 19F NMR (376 MHz, CDCl3) δ −106.42-−107.22 (m, 1F), −107.77 (tdd, J=208.8, 70.6, 8.1 Hz, 2F), −109.34-−109.49 (m, 1F), −131.78 (dd, J=169.8, 1.2 Hz, 1F), −147.38 (dd, J=170.0, 4.6 Hz, 1F); ESIMS m/z 376 ([M+H]+).

후처리

  1. extractionextracted with EtOAc (3×)
  2. customThe combined organic layers were dried
  3. customwere removed under a gentle stream of N2
  4. custompurified by flash chromatography (SiO2, 5-25% EtOAc/Hexanes over 6 min, 25% for 4 min)

출처 및 근거

ORD 기록
ord-893ac0a71b474521b405e40a754c365c
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447073B2

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