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

HRID 706529

反応式

HRID 706529 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+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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 9811564Bis(dibenzylideneacetone)palladium触媒HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl触媒HCID 8028Tetrahydrofuran溶媒

実験手順

A flask was charged with 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 (1.48 g, 3.10 mmol), cesium carbonate (99 g, 588 mmol), and tetrahydrofuran (500 mL) under an atmosphere of dry nitrogen. The mixture was heated at reflux under nitrogen for 7 hours. A further 1 equivalent of cesium carbonate was added and the reaction was 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 twice with ethyl acetate. 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. temperatureThe mixture was heated
  2. temperatureat reflux under nitrogen for 7 hours
  3. temperaturethe reaction was heated a further 7 hours
  4. filtrationfiltered through Celite
  5. washwashed with ethyl acetate
  6. customThe filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate
  7. extractionThe aqueous phase was extracted twice with ethyl acetate
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried with sodium sulfate
  10. concentrationconcentrated under vacuum
  11. custompurified by column chromatography

出典と根拠

ORDレコード
ord-e5eb8aefbb234f7c8e524483f757bdec
出典データセット
uspto-grants-2015_11
特許番号
US09174981B2

関連ノート

読み込み中…