Thionyl Chloride → Methyl 4-chloro-3-fluoropicolinate

HRID 1685336ノート

反応式

HRID 1685336 の反応式
[CH3:1]OCOC1C=CC=CC=1C(C1C=CC=CC=1)=O.[Cl:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([C:26]([O-:28])=[O:27])[C:21]=1[F:29].[Li+].[Br-].[Na+].S(Cl)(Cl)=O>>[Cl:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([C:26]([O:28][CH3:1])=[O:27])[C:21]=1[F:29]

参加物

5

反応物 4

HCID 24386Thionyl Chloride2 回HCID 253881Sodium BromideHCID 10444405(2-(Methoxymethoxy)phenyl)(phenyl)methanoneHCID 67265899Lithium 4-chloro-3-fluoropicolinate

生成物 1

HCID 59200355Methyl 4-chloro-3-fluoropicolinate

反応条件

温度
95 °C

実験手順

The title compound was prepared according to the procedure described in Org. Prep. and Proc. Int., 29 (1), 117-122 (1997). A suspension of lithium 4-chloro-3-fluoropicolinate (20.0 g, 136 mmol) and sodium bromide (28.0 g, 272 mmol, 2 eq) in thionyl chloride (99 mL, 1.36 mmol, 10 eq) was heated to reflux (95° C.) with an argon flush. The reaction was refluxed for 2 days then thionyl chloride (50 mL, 680 mmol, 5 eq) was added again and the reaction was refluxed for 3 more days. The mixture was then evaporated and the residue cooled down to 0° C. Methanol (300 mL) was cautiously added by portions and the mixture was stirred at 23° C. overnight. The reaction was then partitioned into ethyl acetate/sat. aq sodium carbonate and the aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in boiling hexanes and the residual tar was decanted. The filtrate was evaporated to give the title material (24.36 g, 94%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.92 (3H, s), 8.01 (1H, t, J=5.1 Hz), 8.50 (1H, d, J=5.1 Hz). LC/MS (M+H)+: 190.

後処理

  1. temperaturewas heated
  2. customflush
  3. temperatureThe reaction was refluxed for 2 days
  4. temperaturethe reaction was refluxed for 3 more days
  5. customThe mixture was then evaporated
  6. temperaturethe residue cooled down to 0° C
  7. additionMethanol (300 mL) was cautiously added by portions
  8. customThe reaction was then partitioned into ethyl acetate/
  9. extractionaq sodium carbonate and the aqueous phase was extracted with ethyl acetate
  10. dry with materialThe combined organic layers were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. dissolutionThe residue was dissolved
  14. customthe residual tar was decanted
  15. customThe filtrate was evaporated

出典と根拠

ORDレコード
ord-efaf9f867ae842d484dfe7b7064c5372
出典データセット
uspto-grants-2012_04
特許番号
US08148400B2

反応ノート

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