Sodium Bicarbonate → HCID 178419037, compound

HRID 9876

Reaction equation

HRID 9876 reaction equation
Br[C:2]1[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[C:5]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[NH:4][N:3]=1.C([Li])CCC.CCCCCC.[CH2:31]1[CH:39]2[N:34]([CH2:35][CH2:36][C:37](=[O:40])[CH2:38]2)[CH2:33][CH2:32]1.C(=O)([O-])O.[Na+]>O1CCCC1>[F:19][C:16]1[CH:17]=[CH:18][C:13]([C:5]2[NH:4][N:3]=[C:2]([C:37]3([OH:40])[CH2:38][CH:39]4[N:34]([CH2:33][CH2:32][CH2:31]4)[CH2:35][CH2:36]3)[C:6]=2[C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 11240524Octahydroindolizin-7-oneHCID 178418244HCID 178418244, compoundHCID 178418951HCID 178418951, compound

Product 1

HCID 178419037HCID 178419037, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Bromo-5-(4-fluorophenyl)-4-(pyridin-4-yl)pyrazole (3.18 g (10 mmol), prepared as described in 1)) was dissolved in tetrahydrofuran (32 ml). To the solution was added a solution of 1.6 M butyl lithium/hexane (13.75 ml, 13.75 mmol) at −78° C., and the resulting mixture was stirred for 10 minutes. To the mixture was added 1,2,3,5,6,7,8,8a-octahydroindolizin-7-one (1.53 g, 11 mmol) at −78° C., and the resulting mixture was stirred first at −78° C. for 2 hours, then at room temperature for 1 hour. At the end of this time, the reaction mixture was added to a saturated aqueous solution of sodium hydrogencarbonate and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel (eluent, ethyl acetate:methanol:isopropylamine=20:1:1), to give the title compound (830 mg) as a pale yellow powder (yield 22%).

Workup

  1. stirringthe resulting mixture was stirred first at −78° C. for 2 hours
  2. waitat room temperature for 1 hour
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was removed by distillation under reduced pressure
  7. customThe residue was purified by column chromatography through silica gel (eluent, ethyl acetate:methanol:isopropylamine=20:1:1)

Sources & evidence

ORD record
ord-f727051775ed4d1eac90c44fb5a04956
Source dataset
uspto-grants-2006_08
Patent number
US07091352B2

Linked notes

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