Triethylamine → 3-(4-BOC-piperazino)-2-chloropyridine

HRID 220441노트

반응식

HRID 220441 반응식
[Cl:1][C:2]1[C:7](I)=[CH:6][CH:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:7]2[C:2]([Cl:1])=[N:3][CH:4]=[CH:5][CH:6]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 27357432-Chloro-3-iodopyridine

생성물 1

HCID 593218363-(4-BOC-piperazino)-2-chloropyridine수율 54%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

실험 절차

Dissolve 2-chloro-3-iodopyridine (4.00 g, 16.74 mmol) in anhydrous toluene (25 mL). Add piperazine-1-carboxylic acid t-butyl ester (2.96 g, 15.90 mmol), followed by palladium acetate (0.113 g, 0.50 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.313 g, 0.502 mmol), triethylamine (0.034 g, 0.047 mL, 0.335 mmol) and cesium carbonate (27.3 g, 83.7 mmol). Heat at reflux for 18 hr. Concentrate and partition the residue between DCM and a saturated solution of sodium bicarbonate. Extract the aqueous phase twice with DCM and once with ethyl acetate. Dry the combined organic extracts (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 5:95 to 20:80 ethyl acetate:hexanes), to give 4-(2-Chloropyridin-3-yl)-piperazine-1-carboxylic acid t-butyl ester (54%). MS (ES): m/z=298 [M+H].

후처리

  1. temperatureHeat
  2. temperatureat reflux for 18 hr
  3. concentrationConcentrate
  4. custompartition the residue between DCM
  5. extractionExtract the aqueous phase twice with DCM
  6. dry with materialDry the combined organic extracts (sodium sulfate)
  7. filtrationfilter
  8. concentrationconcentrate
  9. custompurify
  10. wash(silica gel chromatography, eluting with 5:95 to 20:80 ethyl acetate:hexanes)

출처 및 근거

ORD 기록
ord-a8066f2c014748939b38035db32aaae5
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202873B2

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