Diisopropylamine → HCID 18975670, compound

HRID 2393465Notes

Reaction equation

HRID 2393465 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH:13]1([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[CH:25]=3)[CH2:20][CH2:19][N:18]=2)[CH2:16][CH2:15][CH2:14]1.Cl[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=1>O1CCCC1>[CH3:28][O:27][C:24]1[CH:25]=[C:26]2[C:21]([CH2:20][CH2:19][N:18]=[C:17]2[C:13]2([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[CH2:14][CH2:15][CH2:16]2)=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 79772-ChloropyridineHCID 18975659HCID 18975659, compoundHCID 178418339Butyllithium

Product 1

HCID 18975670HCID 18975670, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-23 °C

Procedure

n-Butyllithium (7.3 ml, 2.09M in hexanes) was added dropwise at ambient temperature to a solution of diisopropylamine (2.12 ml) in dry tetrahydrofuran (14 ml). After 15 minutes, the solution was cooled to -23° C. and a solution of 1-cyclobutyl-7-methoxy-3,4-dihydroisoquinoline (3 g) in tetrahydrofuran (34 ml) was added. After 30 minutes the mixture was cooled to -78° C., treated with 2-chloropyridine (1.56 ml), stirred for 1 hour then warmed to ambient temperature. The mixture was heated under reflux for 5 minutes, stirred for 16 hours at ambient temperature, then heated under reflux for 30 minutes. The reaction mixture was poured onto water and extracted with ethyl acetate. The extracts were dried and concentrated and the residual orange oil heated at 90° C. at 13.3 mbar to remove excess 2-chloropyridine. The residue was purified by flash chromatography over silica gel using a 5:1 mixture of light petroleum and triethylamine as eluant to give 7-methoxy-1-[1-(2-pyridyl)cyclobutyl]-3,4-dihydroisoquinoline as a solid (0.58 g).

Workup

  1. temperatureAfter 30 minutes the mixture was cooled to -78° C.
  2. temperaturethen warmed to ambient temperature
  3. temperatureThe mixture was heated
  4. temperatureunder reflux for 5 minutes
  5. stirringstirred for 16 hours at ambient temperature
  6. temperatureheated
  7. temperatureunder reflux for 30 minutes
  8. additionThe reaction mixture was poured onto water
  9. extractionextracted with ethyl acetate
  10. customThe extracts were dried
  11. concentrationconcentrated
  12. temperaturethe residual orange oil heated at 90° C. at 13.3 mbar
  13. customto remove excess 2-chloropyridine
  14. customThe residue was purified by flash chromatography over silica gel using
  15. additiona 5:1 mixture of light petroleum and triethylamine as eluant

Sources & evidence

ORD record
ord-51ef2dc186c04549a9c508fa7e71d553
Source dataset
uspto-grants-1998_09
Patent number
US05807868

Reaction notes

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