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

HRID 220445노트

반응식

HRID 220445 반응식
[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]

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
100 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-b6bf382244e44ddeae86586d903d0ba8
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202873B2

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