Dichloromethane → Cyclobutyl{1-[(4-methoxyphenyl)methyl]-3,4,5,6,7,8-hexahydroisoquinolin-2(1H)-yl}methanone

HRID 1390541Notes

Reaction equation

HRID 1390541 reaction equation
C(N(CC)CC)C.Cl.[CH3:9][O:10][C:11]1[CH:27]=[CH:26][C:14]([CH2:15][CH:16]2[C:25]3[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=3[CH2:19][CH2:18][NH:17]2)=[CH:13][CH:12]=1.C(Cl)Cl.[CH:31]1([C:35](Cl)=[O:36])[CH2:34][CH2:33][CH2:32]1>O>[CH:31]1([C:35]([N:17]2[CH2:18][CH2:19][C:20]3[CH2:21][CH2:22][CH2:23][CH2:24][C:25]=3[CH:16]2[CH2:15][C:14]2[CH:13]=[CH:12][C:11]([O:10][CH3:9])=[CH:27][CH:26]=2)=[O:36])[CH2:34][CH2:33][CH2:32]1

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 78705Cyclobutanecarbonyl chlorideHCID 2133280070234-85-4

Product 1

HCID 3024050Cyclobutyl{1-[(4-methoxyphenyl)methyl]-3,4,5,6,7,8-hexahydroisoquinolin-2(1H)-yl}methanone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Triethylamine (22.2 g., 0.22 mole) is slowly added to 1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline hydrochloride Ia (29.4 g., 0.1 mole) dissolved in 200 ml. of methylene chloride with stirring and ice-bath cooling. Cyclobutylcarbonyl chloride (13 g., 0.107 mole) in 30 ml. of methylene chloride is then added dropwise with stirring to the mixture while maintaining a temperature of 0° to 5° C. After stirring the reaction mixture for 1 hr. at room temperature, 100 ml. of water is added, the mixture acidified by adding 50 ml. of 10% sulfuric acid, and the methylene chloride layer separated. If desired, the methylene chloride solution containing IIa can be used for the next step directly or concentrated to give an oil which solidifies upon standing. Recrystallization of a sample of the solidified material from acetone provides crystalline product IIa, m.p. 89°-91°.

Workup

  1. dissolutiondissolved in 200 ml
  2. temperatureice-bath cooling
  3. temperaturewhile maintaining a temperature of 0° to 5° C
  4. stirringAfter stirring the reaction mixture for 1 hr
  5. customat room temperature
  6. additionby adding 50 ml
  7. customof 10% sulfuric acid, and the methylene chloride layer separated
  8. additionthe methylene chloride solution containing IIa
  9. concentrationconcentrated
  10. customto give an oil which
  11. customRecrystallization of a sample of the solidified material from acetone
  12. customprovides crystalline product IIa, m.p. 89°-91°

Sources & evidence

ORD record
ord-34b2f762578d44d7bdde522816c9e3e4
Source dataset
uspto-grants-1979_02
Patent number
US04139534

Reaction notes

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