Diethyl Ether → Methyl 3-azido-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate

HRID 2410866ノート

反応式

HRID 2410866 の反応式
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)(=[O:20])=[O:19])=[CH:14][CH:13]=2)=[N:10][C:9]([Br:27])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].[N-:32]=[N+:33]=[N-].[Na+].CCOCC>C(O)(C(F)(F)F)=O.O>[N:1]([C:2]1[C:11]([C:12]2[CH:13]=[CH:14][C:15]([S:18]([N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)(=[O:19])=[O:20])=[CH:16][CH:17]=2)=[N:10][C:9]([Br:27])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[N+:32]=[N-:33]

参加物

7

反応物 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 86663067Methyl 3-amino-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate

生成物 1

HCID 86663068Methyl 3-azido-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate収率 88%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6422Trifluoroacetic acid溶媒

実験手順

Methyl 3-amino-6-bromo-2-(4-(morpholinosulfonyl)phenyl)-isonicotinate (0.988 g, 2.17 mmol) was dissolved in TFA (11 mL) and the yellow solution was cooled in an ice bath. Powdered sodium nitrite (0.299 g, 4.33 mmol) was added with stirring to give a dark red mixture with gas evolution. After 20 min, powdered sodium azide (1.41 g, 21.7 mmol) was added over 5 min followed by Et2O (11 mL). A thick precipitate formed and, after 30 min, water was added and the mixture was extracted with EtOAc. The organic phase was washed with water (3×), brine (1×), saturated aqueous Na2CO3 solution (so that the aqueous phase was basic), and brine. After drying the solvent with sodium sulfate, the solvent was removed and silica gel chromatography (step gradient elution with DCM containing 0 to 10% EtOAc) afforded methyl 3-azido-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate (918 mg, 1.90 mmol, 88% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 7.93-7.96 (2H, m), 7.87 (1H, s), 7.85 (2H, d, J=8.24 Hz), 4.03 (3H, s), 3.73-3.77 (4H, m), 3.03-3.07 (4H, m).

後処理

  1. temperaturethe yellow solution was cooled in an ice bath
  2. customto give a dark red mixture with gas evolution
  3. customA thick precipitate formed and, after 30 min
  4. extractionthe mixture was extracted with EtOAc
  5. washThe organic phase was washed with water (3×), brine (1×), saturated aqueous Na2CO3 solution (so that the aqueous phase
  6. dry with materialAfter drying the solvent with sodium sulfate
  7. customthe solvent was removed
  8. washsilica gel chromatography (step gradient elution with DCM containing 0 to 10% EtOAc)

出典と根拠

ORDレコード
ord-afbcf43adcc34cbf839c97e1377aad6f
出典データセット
uspto-grants-2014_08
特許番号
US08815840B2

反応ノート

読み込み中…