碳酸氢铯 → TERT-BUTYL (4-FLUOROPYRIDIN-2-YL)CARBAMATE

HRID 79419

反应方程式

HRID 79419 反应方程式
Cl[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][N:3]=1.[C:9](=[O:16])([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[NH2:10].C(=O)([O-])[O-].[Cs+].[Cs+]>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.O1CCCC1>[F:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:10][C:9](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:7]=1

参与物

7

反应物 3

HCID 10796碳酸氢铯2 次HCID 77922氨基甲酸叔丁酯HCID 27827922-氯-4-氟吡啶

产物 1

HCID 51354888TERT-BUTYL (4-FLUOROPYRIDIN-2-YL)CARBAMATE收率 70.1%

试剂、催化剂与溶剂 3

HCID 9832798Tris(dibenzylideneacetone) dipalladium催化剂HCID 111557942-二环己基膦-2',4',6'-三异丙基联苯催化剂HCID 8028四氢呋喃溶剂

实验过程

A 2 L flask was charged 2-chloro-4-fluoropyridine (20 g, 152 mmol), tert-butyl carbamate (89 g, 760 mmol), tris(dibenzylideneacetone) dipalladium (1.39 g, 1.52 mmol), X-PHOS (2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-1,1′-biphenyl) (1.48 g, 3.10 mmol), cesium carbonate (99 g, 588 mmol), and tetrahydrofuran (500 mL) under an atmosphere of dry nitrogen. This mixture was heated at reflux under nitrogen for 7 hours. An additional 1 equivalent of cesium carbonate was added to drive the reaction to completion (heated a further 7 hours). The mixture was cooled to ambient temperature, filtered through Celite and washed with ethyl acetate. The filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate. The aqueous phase was extracted with ethyl acetate twice. The combined organic phases were washed with brine and dried with sodium sulfate, concentrated under vacuum, and purified by column chromatography to give tert-butyl 4-fluoropyridin-2-ylcarbamate as a pale yellow solid (22.6 g).

后处理

  1. temperatureThis mixture was heated
  2. temperatureat reflux under nitrogen for 7 hours
  3. customthe reaction to completion (
  4. temperatureheated a further 7 hours)
  5. filtrationfiltered through Celite
  6. washwashed with ethyl acetate
  7. customThe filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate
  8. extractionThe aqueous phase was extracted with ethyl acetate twice
  9. washThe combined organic phases were washed with brine
  10. dry with materialdried with sodium sulfate
  11. concentrationconcentrated under vacuum
  12. custompurified by column chromatography

来源与证据

ORD记录
ord-1968fdd3c2b6421f94b4cfb6dae4529a
来源数据集
uspto-grants-2014_09
专利号
US08841455B2

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