5-Bromo-2-furanecarboxylic acid → HCID 952706, compound

HRID 891430Notes

Reaction equation

HRID 891430 reaction equation
Cl.Cl.[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH2:11])[CH2:4]2.[Br:12][C:13]1[O:17][C:16]([C:18](O)=[O:19])=[CH:15][CH:14]=1.O.ON1C2C=CC=CC=2N=N1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH:11][C:18]([C:16]1[O:17][C:13]([Br:12])=[CH:14][CH:15]=1)=[O:19])[CH2:4]2

Participants

7

Reactant 5

HCID 685115-Bromo-2-furanecarboxylic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27960291-Hydroxybenzotriazole hydrateHCID 12494972(R)-(+)-3-Aminoquinuclidine Dihydrochloride

Product 1

HCID 952706HCID 952706, compoundYield 54.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (R)-1-azabicyclo[2.2.2]oct-3-ylamine dihydrochloride (655 mg), 5-bromofuran-2-carboxylic acid (681 mg), 1-hydroxybenzotriazole hydrate (457 mg), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.069 g), and N,N-diisopropylethylamine (2.5 mL) in N,N-dimethylformamide (10 mL) was agitated until a homogenous solution was obtained, and was then allowed to stand at room temperature overnight. The solution was evaporated, and the residue was partitioned between aqueous sodium hydroxide and chloroform. The chloroform layer was dried over magnesium sulfate, filtered, and evaporated and the residue was purified by chromatography on silica gel in a solid phase extraction cartridge using ammoniated methanol/chloroform mixtures as the eluent. The compound was then dissolved in tetrahydrofuran (20 mL), excess hydrogen chloride (5 mL; 1 M solution in diethyl ether) was added, and the solution was evaporated and then recrystallised from methanol/diethyl ether to give the hydrochloride salt of the title compound as a colourless solid (538 mg); MS (ES+) 299, 301 (MH+).

Workup

  1. customwas obtained
  2. customThe solution was evaporated
  3. customthe residue was partitioned between aqueous sodium hydroxide and chloroform
  4. dry with materialThe chloroform layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customthe residue was purified by chromatography on silica gel in a solid phase extraction cartridge
  8. dissolutionThe compound was then dissolved in tetrahydrofuran (20 mL)
  9. additionexcess hydrogen chloride (5 mL; 1 M solution in diethyl ether) was added
  10. customthe solution was evaporated
  11. customrecrystallised from methanol/diethyl ether

Sources & evidence

ORD record
ord-95b5f8b75f0a405a8fa62cba0581ace3
Source dataset
uspto-grants-2006_02
Patent number
US07001914B2

Reaction notes

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