Potassium Carbonate → 4-[2-(2-Fluoro-phenyl)-pyridin-3-yl]-piperazine-1-carboxylic acid t-butyl ester

HRID 220445ノート

反応式

HRID 220445 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15](Cl)=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[F:21])=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 593218363-(4-BOC-piperazino)-2-chloropyridine

生成物 1

HCID 687242774-[2-(2-Fluoro-phenyl)-pyridin-3-yl]-piperazine-1-carboxylic acid t-butyl ester収率 91%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
100 °C

実験手順

Dissolve 4-(2-chloropyridin-3-yl)-piperazine-1-carboxylic acid t-butyl ester (0.9 g, 3.0 mmol) in a mixture of 5 mL 1,2 dimethoxyethane and 4 mL water. Add 2-fluorophenylboronic acid (0.51 g, 3.64 mmol) followed by tetrakis(triphenylphosphine) palladium(0) (0.35 g, 0.30 mmol), and potassium carbonate (1.13 g, 8.2 mmol). Heat the reaction mixture at 100° C. for 22 hr. Cool to room temperature, concentrate and partition the residue between ethyl acetate and water. Extract water layer with ethyl acetate. Wash combined organic layers with brine. Dry organic extracts (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 10:90 to 30:70 ethyl acetate:hexanes), to give 4-[2-(2-Fluoro-phenyl)-pyridin-3-yl]-piperazine-1-carboxylic acid t-butyl ester (91%). MS (ES): m/z=358 [M+H]+.

後処理

  1. temperatureCool to room temperature
  2. concentrationconcentrate
  3. custompartition the residue between ethyl acetate and water
  4. washWash
  5. filtrationDry organic extracts (sodium sulfate), filter
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 10:90 to 30:70 ethyl acetate:hexanes)

出典と根拠

ORDレコード
ord-b6bf382244e44ddeae86586d903d0ba8
出典データセット
uspto-grants-2012_06
特許番号
US08202873B2

反応ノート

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