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

HRID 79419

반응식

HRID 79419 반응식
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

참가 물질

7

반응물 3

HCID 10796Cesium carbonate2회HCID 77922tert-Butyl carbamateHCID 27827922-Chloro-4-fluoropyridine

생성물 1

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

시약·촉매·용매 3

HCID 9832798Tris(dibenzylideneacetone) dipalladium촉매HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl촉매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-1968fdd3c2b6421f94b4cfb6dae4529a
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841455B2

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