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

HRID 40699Notes

Reaction equation

HRID 40699 reaction equation
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]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 433294Lithium ChlorideHCID 226480948-Boc-3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-3-ene2×HCID 672487012-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]pyridine

Product 1

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

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-918059c66a0a4340975e82897c69135e
Source dataset
uspto-grants-2013_09
Patent number
US08530477B2

Reaction notes

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