Potassium Phosphate, Tribasic → 4-Fluoro-2-(2-nitro-5-(piperidin-1-yl)phenyl)pyridine

HRID 625387ノート

反応式

HRID 625387 の反応式
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:6][C:5]=1B1OC(C)(C)C(C)(C)O1)([O-:3])=[O:2].Cl[C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][N:27]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:32][C:30]1[CH:29]=[CH:28][N:27]=[C:26]([C:5]2[CH:6]=[C:7]([N:10]3[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]3)[CH:8]=[CH:9][C:4]=2[N+:1]([O-:3])=[O:2])[CH:31]=1

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 27827922-Chloro-4-fluoropyridineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 66587487HCID 66587487、化合物

生成物 1

HCID 665867694-Fluoro-2-(2-nitro-5-(piperidin-1-yl)phenyl)pyridine収率 58.8%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 18180031Water 1,2-dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

Into a 500-mL 3-necked round bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1-(4-nitro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine (15 g, 45.18 mmol, 1.00 equiv) in DME/H2O (100/5 mL), 2-chloro-4-fluoropyridine (7.80 g, 60.00 mmol, 1.20 equiv), K3PO4 (31 g, 146.23 mmol, 3.00 equiv), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (SPhos) (2.00 g, 4.88 mmol, 0.10 equiv), and Pd(PPh3)4 (2800 mg, 2.42 mmol, 0.05 equiv). The resulting solution was stirred for 1 overnight at 80° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 200 mL of H2O, extracted with 3×300 mL of dichloromethane, and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (10:1). The product was obtained as 8 g of a yellow solid.

後処理

  1. customInto a 500-mL 3-necked round bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. additionThe resulting solution was diluted with 200 mL of H2O
  5. extractionextracted with 3×300 mL of dichloromethane
  6. washThe resulting mixture was washed with 1×20 mL of brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. washeluted with ethyl acetate/petroleum ether (10:1)

出典と根拠

ORDレコード
ord-ea9d29b0e95e4d339266004b41c012a9
出典データセット
uspto-grants-2016_04
特許番号
US09301951B2

反応ノート

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