Potassium Carbonate → 3-[4-(Pyridin-2-yl-oxy)phenyl]-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester

HRID 40699노트

반응식

HRID 40699 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:21]=[CH:20][C:12]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[CH:11][CH:10]=2)O1.[C:23]([O:27][C:28]([N:30]1[CH:35]2[CH2:36][CH2:37][CH:31]1[CH:32]=[C:33](OS(C(F)(F)F)(=O)=O)[CH2:34]2)=[O:29])([CH3:26])([CH3:25])[CH3:24].[Cl-].[Li+].C([O-])([O-])=O.[K+].[K+]>COCCOC.[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(OCC)(=O)C>[C:23]([O:27][C:28]([N:30]1[CH:35]2[CH2:36][CH2:37][CH:31]1[CH:32]=[C:33]([C:9]1[CH:10]=[CH:11][C:12]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[CH:20][CH:21]=1)[CH2:34]2)=[O:29])([CH3:26])([CH3:24])[CH3:25]

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 433294Lithium ChlorideHCID 226480948-Boc-3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-3-ene2회HCID 672487012-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]pyridine

생성물 1

HCID 674124983-[4-(Pyridin-2-yl-oxy)phenyl]-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester수율 56.6%

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

실험 절차

2-[4-(4,4,5,5-Tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxy]pyridine (0.62 g, 2.1 mmol), 3-trifluoromethanesulfonyloxy-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester (0.75 g, 2.1 mmol) (intermediate 1), tetrakis(triphenylphosphine)-palladium (0.24 g, 0.21 mmol) and lithium chloride (0.107 g, 2.52 mmol) are placed in 10 ml of DME and 2.6 ml of a 2N aqueous solution of K2CO3. The reaction medium is refluxed for 16 h. After hydrolysis and extraction with ethyl acetate, the organic phase is dried over MgSO4 and concentrated to dryness. The crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of ethyl acetate in heptane ranging from 0% to 30%. 0.45 g of expected 3-[4-(pyridin-2-yl-oxy)phenyl]-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester is obtained.

후처리

  1. temperatureThe reaction medium is refluxed for 16 h
  2. dry with materialthe organic phase is dried over MgSO4
  3. concentrationconcentrated to dryness
  4. customThe crude product obtained
  5. customis chromatographed on silica gel, elution

출처 및 근거

ORD 기록
ord-918059c66a0a4340975e82897c69135e
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530477B2

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