Diethyl Ether → Methyl 3-azido-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate

HRID 2410740노트

반응식

HRID 2410740 반응식
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([O:20][CH3:21])=[O:19])=[CH:14][CH:13]=2)=[N:10][C:9]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([F:30])[CH:23]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].[N-:35]=[N+:36]=[N-].[Na+].C(OCC)C>FC(F)(F)C(O)=O>[N:1]([C:2]1[C:11]([C:12]2[CH:13]=[CH:14][C:15]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:17]=2)=[N:10][C:9]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([F:30])[CH:23]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[N+:35]=[N-:36]

참가 물질

6

반응물 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 66604696Methyl 3-amino-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate

생성물 1

HCID 86663018Methyl 3-azido-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate수율 99.5%

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

실험 절차

Methyl 3-amino-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)-isonicotinate (1.00 g, 2.44 mmol) was dissolved in trifluoroacetic acid (12 mL) and the yellow solution was cooled in an ice bath. Powdered sodium nitrite (0.336 gm, 4.87 mmol) was added with stirring to give a dark red mixture. After 30 min, powdered sodium azide (1.59 g, 24.4 mmol) was added followed by diethyl ether (12 mL). The light red mixture was stirred in the ice bath for 30 min. The reaction was partitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution) to neutralize the acid. The organic phase was washed with brine, dried with sodium sulfate, and the solvent removed. Flash silica gel chromatography (elution with a 1:1 mixture of methylene chloride and EtOAc) afforded methyl 3-azido-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate (1.06 gm). 1H NMR (CDCl3) δ ppm 8.17 (2H, d, J=7.93 Hz), 8.01 (1H, s), 7.91 (2H, d, J=7.93 Hz), 7.82-7.88 (1H, m), 7.79 (1H, d, J=8.55 Hz), 7.04 (1H, t, J=8.55 Hz), 4.05 (3H, s), 3.96 (3H, s), 3.94 (3H, s).

후처리

  1. temperaturethe yellow solution was cooled in an ice bath
  2. customto give a dark red mixture
  3. customThe reaction was partitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution)
  4. washThe organic phase was washed with brine
  5. dry with materialdried with sodium sulfate
  6. customthe solvent removed
  7. washFlash silica gel chromatography (elution
  8. additionwith a 1:1 mixture of methylene chloride and EtOAc)

출처 및 근거

ORD 기록
ord-d72d954cbb17401db96de4beba57a824
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815840B2

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