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

HRID 1508498

반응식

HRID 1508498 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 962Water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d246f0488f5b47a8ab278887cef78feb
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221834B2

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