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

HRID 60234

反応式

HRID 60234 の反応式
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]

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 9832798Tris(dibenzylideneacetone) dipalladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
85 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-2aad88eff7364f1f9f9968439896e0fc
出典データセット
uspto-grants-2016_09
特許番号
US09440976B2

関連ノート

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