2,4-Dimethoxybenzoic acid → HCID 45381408, compound

HRID 2088315Notes

Reaction equation

HRID 2088315 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][O:11][C:12]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:13]=1[C:14]([OH:16])=O.Cl.Cl.[NH2:25][C@H:26]1[CH:31]2[CH2:32][CH2:33][N:28]([CH2:29][CH2:30]2)[CH2:27]1.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[OH-].[Na+]>CN(C=O)C>[CH3:10][O:11][C:12]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:13]=1[C:14]([NH:25][C@H:26]1[CH:31]2[CH2:32][CH2:33][N:28]([CH2:29][CH2:30]2)[CH2:27]1)=[O:16]

Participants

7

Reactant 5

HCID 70522,4-Dimethoxybenzoic acidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 12494973(3S)-1-azabicyclo[2.2.2]octan-3-amine dihydrochlorideHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium

Product 1

HCID 45381408HCID 45381408, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4.0 ml of DMF, N,N′-Diisopropylethylamine (5.6 ml, 32.14 mmol), and 2,4-Dimethoxybenzoic acid (1.75 g, 9.64 mmol) was added to a flask charged with (S)-(−)-3-Aminoquinuclidine dihydrochloride (1.60 g, 8.03 mmol) and stirred ice-water bath under nitrogen atmosphere. To the mixture was added 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium (3.05 g, 8.03 mmol) then mixture temperature was raised to ambient temperature slowly by removing the ice-water bath for 60 minutes. Reaction mixture was worked up by addition of 1N sodium hydroxide aqueous solution and extracted twice with ethyl acetate, combined organic layer was washed with saturated brine solution, dried over sodium sulfate, filtered, and concentrated to crude clear oil. Purification via preparative HPLC to obtain pure product of (S)-2,4-dimethoxy-N-(quinuclidin-3-yl)benzamide, (1.95 g, 84% yield) 1H NMR (400 MHz, Methanol-D4) δ (ppm): 7.42 (m, 1H), 7.11 (s, 2H), 4.45 (m, 1H), 3.95 (s, 3H), 3.83 (m, 1H), 3.80 (s, 3H), 3.39-3.27 (m, 5H), 2.37 (m, 1H), 2.19 (m, 1H), 2.11 (m, 2H), 2.01 (m, 1H). C16H22N2O3 =290.16 LCMS (M+H): m/z 291

Workup

  1. customby removing the ice-water bath for 60 minutes
  2. customReaction mixture
  3. extractionextracted twice with ethyl acetate
  4. washwas washed with saturated brine solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to crude clear oil
  8. customPurification via preparative HPLC

Sources & evidence

ORD record
ord-ff22345c018b4389b6be811e890394e4
Source dataset
uspto-grants-2013_05
Patent number
US08435762B2

Reaction notes

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