Cesium carbonate → tert-butyl N-(4-fluoropyridin-2-yl)carbamate

HRID 79247

反応式

HRID 79247 の反応式
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

参加物

7

反応物 3

HCID 10796Cesium carbonate2 回HCID 77922tert-Butyl carbamateHCID 27827922-Chloro-4-fluoropyridine

生成物 1

HCID 51354888tert-butyl N-(4-fluoropyridin-2-yl)carbamate収率 70.1%

試薬・触媒・溶媒 3

HCID 9832798Tris(dibenzylideneacetone) dipalladium触媒HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl触媒HCID 8028Tetrahydrofuran溶媒

実験手順

To 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. A further 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).

後処理

  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

出典と根拠

ORDレコード
ord-49adccde2ee24f8e8aa65af08f469fc0
出典データセット
uspto-grants-2014_09
特許番号
US08841455B2

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