Morpholine → HCID 70497089, compound

HRID 2407973Notes

Reaction equation

HRID 2407973 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=1)[CH2:9][C:8]12[CH2:25][CH2:24][CH2:23][CH2:22]1)=[O:4].[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[CH:16]=1)[CH2:9][C:8]12[CH2:25][CH2:24][CH2:23][CH2:22]1)=[O:4]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 70495943HCID 70495943, compound

Product 1

HCID 70497089HCID 70497089, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture solution of 2′-(3-bromo-phenyl)-2′,3′-dihydro-1′H-spiro[cyclopentane-1,4′-quinoline]-6′-carboxylic acid methyl ester (600 mg, 1.5 mmol), morpholine (2.6 mL, 29.4 mmol), copper(I) iodide (340 mg, 1.8 mmol), N,N-dimethylglycine hydrochloride (340 mg, 2.4 mmol), and potassium carbonate (1.2 g, 9.0 mmol) in dimethyl sulfoxide (6.5 mL) was stirred at 120° C. for 16 h. Then the reaction mixture was cooled to room temperature. The reaction mixture was extracted with ethyl acetate (200 mL×2), washed with saturated aqueous ammonium chloride solution (50 mL×3) and brine (50 mL×2), dried over anhydrous sodium sulfate and then concentrated in vacuo and the residue was purified by ISCO combi-flash chromatography (gradient elution, 30-50% ethyl acetate in petroleum ether) to afford 2′-(3-morpholinophenyl)-2′,3′-dihydro-1′H-spiro[cyclopentane-1,4′-quinoline]-6′-carboxylic acid methyl ester (487.2 mg, 80%) as a white solid: MS (ESI) M+1=407.0.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate (200 mL×2)
  2. washwashed with saturated aqueous ammonium chloride solution (50 mL×3) and brine (50 mL×2)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customthe residue was purified by ISCO combi-flash chromatography (gradient elution, 30-50% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-7cfbd7e53bd7445f94240a45f40f430a
Source dataset
uspto-grants-2014_08
Patent number
US08809369B2

Reaction notes

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