Cesium carbonate → Tert-butyl (6-chloro-5-fluoropyridin-3-yl)carbamate

HRID 60234

반응식

HRID 60234 반응식
Br[C:2]1[CH:3]=[C:4]([F:9])[C:5]([Cl:8])=[N:6][CH:7]=1.[C:10](=[O:17])([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[NH2:11].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[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.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[C:13]([O:12][C:10](=[O:17])[NH:11][C:2]1[CH:7]=[N:6][C:5]([Cl:8])=[C:4]([F:9])[CH:3]=1)([CH3:16])([CH3:15])[CH3:14]

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 27632855-Bromo-2-chloro-3-fluoropyridine

생성물 1

HCID 86656040Tert-butyl (6-chloro-5-fluoropyridin-3-yl)carbamate수율 86%

시약·촉매·용매 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매HCID 9832798Tris(dibenzylideneacetone) dipalladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
85 °C

실험 절차

A degassed mixture of 5-bromo-2-chloro-3-fluoropyridine (22.5 g, 107 mmol), tert-butyl carbamate (13.8 g, 117.5 mmol), tris(dibenzylideneacetone) dipalladium(0) (2.95 g, 3.2 mmol), XantPhos (2.48 g, 4.28 mmol) and cesium carbonate (69.7 g, 214 mmol) in dioxane (340 mL) was heated at 85° C. for 24 hours. The reaction mixture was cooled to ambient temperature and the resultant solid was removed by filtration. The resultant solid was washed with ethyl acetate followed by dichloromethane and the filtrate was combined and concentrated in-vacuo to afford a residue that was purified by flash chromatography (silica: cyclohexane to 25% ethyl acetate/cyclohexane) to afford the title compound as a pale yellow solid (22.6 g, 86%). 1H NMR (300 MHz, CDCl3): 8.04 (dd, J=10.1, 2.4 Hz, 1H), 7.98 (d, J=2.4 Hz, 1H), 6.62 (s, 1H), 1.53 (s, 9H).

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe resultant solid was removed by filtration
  3. washThe resultant solid was washed with ethyl acetate
  4. concentrationconcentrated in-vacuo
  5. customto afford a residue that
  6. customwas purified by flash chromatography (silica: cyclohexane to 25% ethyl acetate/cyclohexane)

출처 및 근거

ORD 기록
ord-2aad88eff7364f1f9f9968439896e0fc
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440976B2

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