Hydrochloric Acid → 3-Bromo-6-chloro-2-methylpyridine

HRID 1508498

反応式

HRID 1508498 の反応式
N[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([Br:9])=[CH:4][CH:3]=1.N([O-])=O.[Na+].[ClH:14]>O>[Br:9][C:5]1[C:6]([CH3:8])=[N:7][C:2]([Cl:14])=[CH:3][CH:4]=1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 1706782-Pyridinamine, 5-bromo-6-methyl-HCID 23668193Sodium Nitrite

生成物 1

HCID 148666743-Bromo-6-chloro-2-methylpyridine

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

A solution of 6-amino-3-bromo-2-methylpyridine (239 g, 1278 mmol) in concentrated HCl (1.0 L) was cooled to −5° C. A solution of sodium nitrite (238 g, 3450 mmol) in water (1.0 L) was added dropwise over 1 hour while maintaining the temperature of the reaction between −5 and 5° C. After the addition was complete, the reaction was stirred for 1 hour, and then the cooling bath was removed and the reaction was warmed to r.t. and stirred for 16 hours. The reaction was then poured onto ice and 5N NaOH (1.7 L) was added to adjust the pH of the solution to 13. The mixture was extracted 3 times with EtOAc (3 L and 2×2 L). The combined organic layers were dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with 100% methylene chloride afforded 3-bromo-6-chloro-2-methylpyridine. 1H NMR (CDCl3, 500 MHz) δ 7.76 (d, J=8.2 Hz, 1H), 7.07 (d, J=8.1 Hz, 1H), 2.66 (s, 3H).

後処理

  1. temperaturewhile maintaining
  2. customthe temperature of the reaction between −5 and 5° C
  3. additionAfter the addition
  4. customthe cooling bath was removed
  5. stirringstirred for 16 hours
  6. additionThe reaction was then poured onto ice and 5N NaOH (1.7 L)
  7. additionwas added
  8. extractionThe mixture was extracted 3 times with EtOAc (3 L and 2×2 L)
  9. dry with materialThe combined organic layers were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification of the residue by flash chromatography on silica gel with 100% methylene chloride

出典と根拠

ORDレコード
ord-d246f0488f5b47a8ab278887cef78feb
出典データセット
uspto-grants-2015_12
特許番号
US09221834B2

関連ノート

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