Hydrochloric Acid → HCID 15656873, compound

HRID 2396010Notes

Reaction equation

HRID 2396010 reaction equation
[CH2:1]([Li])CCC.[N:6]12[CH2:13][CH2:12][CH:9]([CH2:10][CH2:11]1)[C@H:8]([NH:14][C:15](=[O:25])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[C:17]=1[CH3:24])[CH2:7]2.CN(C)C=O.Cl>CCCCCC.O1CCCC1>[N:6]12[CH2:11][CH2:10][CH:9]([CH2:12][CH2:13]1)[C@H:8]([N:14]1[CH:1]=[CH:24][C:17]3[C:16](=[CH:21][CH:20]=[CH:19][C:18]=3[O:22][CH3:23])[C:15]1=[O:25])[CH2:7]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 15656843HCID 15656843, compoundHCID 178418339Butyllithium

Product 1

HCID 15656873HCID 15656873, compoundYield 92.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of n-butyllithium (2.2 mmol) in hexane was added in a dropwise fashion to a stirred solution of (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-3-methoxy-2-methylbenzamide (0.24 g, 0.87 mmol), from Example 1, Method B, in dry tetrahydrofuran (1.0 mL) at -70° C. The mixture was maintained at -10° C. and stirred for 1 hour. The mixture was then cooled to -70° C. and dimethylformamide (0.1 mL) added. The reaction mixture was allowed to warmto room temperature over 1.5 hours, then cooled to 0° C. and acidified with aqueous hydrochloric acid (10%). The layers were separated and the aqueous phase was washed with ethyl acetate. The aqueous layer wasthen made basic with aqueous sodium hydroxide (10N) and extracted with ethyl acetate (3×50 mL). The combined organic phase was dried over anhydrous sodium sulfate and filtered. Evaporation of solvents gave (S)-2-(1-azabicyclo[2.2.2]oct-3-yl)-5-methoxy-1 (2H)-isoquinolinone as a white solid (0.23 g, 0.804 mmol). Preparation of the hydrochloride salt from ethanol-hydrogen chloride gave (S)-2-(1-azabicyclo[2.2.2]oct-3-yl)-5-methoxyl-1(2H)-isoquinolinone hydrochloride, m.p. 275°-277° C., [α]D25 -106.7° (c=0.30, H2O).

Workup

  1. temperatureThe mixture was then cooled to -70° C.
  2. waitto warmto room temperature over 1.5 hours
  3. temperaturecooled to 0° C.
  4. customThe layers were separated
  5. washthe aqueous phase was washed with ethyl acetate
  6. extractionextracted with ethyl acetate (3×50 mL)
  7. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customEvaporation of solvents

Sources & evidence

ORD record
ord-53c85f8d30c54873bdb1e846da446f59
Source dataset
uspto-grants-1996_02
Patent number
US05491148

Reaction notes

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