(S)-quinuclidin-3-amine → HCID 15656843, compound

HRID 2396008Notes

Reaction equation

HRID 2396008 reaction equation
C[Al](C)C.[NH2:5][C@H:6]1[CH:11]2[CH2:12][CH2:13][N:8]([CH2:9][CH2:10]2)[CH2:7]1.[CH3:14][O:15][C:16]1[C:17]([CH3:26])=[C:18]([CH:23]=[CH:24][CH:25]=1)[C:19](OC)=[O:20]>C1(C)C=CC=CC=1>[N:8]12[CH2:13][CH2:12][CH:11]([CH2:10][CH2:9]1)[C@H:6]([NH:5][C:19](=[O:20])[C:18]1[CH:23]=[CH:24][CH:25]=[C:16]([O:15][CH3:14])[C:17]=1[CH3:26])[CH2:7]2

Participants

5

Reactant 3

HCID 719216(S)-quinuclidin-3-amineHCID 12527049Methyl 3-methoxy-2-methylbenzoateHCID 16682925Trimethylaluminum

Product 1

HCID 15656843HCID 15656843, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of trimethylaluminum (0.8 mmol) in toluene was slowly added to asolution of (S)-3-amino-1-azabicyclo[2.2.2]octane (0.1 g; 0.8 mmol) in toluene (5.0 mL) and the mixture stirred for 15 minutes. A solution of methyl 3-methoxy-2-methylbenzoate (0.1 g; 0.55 mmol) in toluene (2 mL) wasadded and the reaction mixture heated to reflux until, as indicated by thin-layer chromatography, the reaction had finished. The mixture was cooled to 0° C. and then carefully quenched with water (0.4 mL). The reaction mixture was stirred for an additional 30 minutes and then filtered washing with ethyl acetate (2×20 mL). Removal of the solvent from the combined filtrate gave (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-3-methoxy-2-methylbenzamide as a whitesolid (0.19 g, 0.686 mmol). Preparation of the hydrochloride salt from ethanol-hydrogen chloride gave (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-3-methoxy-2-methylbenzamide hydrochloride, m.p. 259°-261° C., [α]D25 -13.8° (c=0.16, H2O).

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureto reflux until,
  3. customcarefully quenched with water (0.4 mL)
  4. stirringThe reaction mixture was stirred for an additional 30 minutes
  5. filtrationfiltered
  6. washwashing with ethyl acetate (2×20 mL)
  7. customRemoval of the solvent from the combined filtrate

Sources & evidence

ORD record
ord-e209af2b5ebb41d2ae718dbfbadc9d96
Source dataset
uspto-grants-1996_02
Patent number
US05491148

Reaction notes

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