Dicyclohexylcarbodiimide → 5,5-Dimethyl-10-[2-methyl-4-(morpholino)butyryloxy]-8-(3-methyl-2-octyl)-2-(2-propynyl)-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-d]pyridine dihydrochloride

HRID 441888Notes

Reaction equation

HRID 441888 reaction equation
[CH3:1][C:2]1([CH3:29])[C:21]2[CH2:22][CH2:23][N:24]([CH2:26][C:27]#[CH:28])[CH2:25][C:20]=2[C:5]2[C:6]([OH:19])=[CH:7][C:8]([CH:10]([CH:12]([CH3:18])[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH3:11])=[CH:9][C:4]=2[O:3]1.[ClH:30].[CH3:31][CH:32]([CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1)[C:33](O)=[O:34].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[ClH:30].[ClH:30].[CH3:29][C:2]1([CH3:1])[C:21]2[CH2:22][CH2:23][N:24]([CH2:26][C:27]#[CH:28])[CH2:25][C:20]=2[C:5]2[C:6]([O:19][C:33](=[O:34])[CH:32]([CH3:31])[CH2:36][CH2:37][N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)=[CH:7][C:8]([CH:10]([CH:12]([CH3:18])[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH3:11])=[CH:9][C:4]=2[O:3]1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 990408-(1,2-Dimethylheptyl)-1,3,4,5-tetrahydro-5,5-dimethyl-2-(2-propyn-1-yl)-2H-(1)benzopyrano(4,3-c)pyridin-10-olHCID 681179462-Methyl-4-morpholinobutyric acid hydrochloride

Product 1

HCID 214181385,5-Dimethyl-10-[2-methyl-4-(morpholino)butyryloxy]-8-(3-methyl-2-octyl)-2-(2-propynyl)-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-d]pyridine dihydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A combination of 5.0 g. (12.6 mmole) of 5,5-dimethyl-10-hydroxy-8-(3-methyl-2-octyl)-2-(2-propynyl)1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-d]pyridine, 2.82 g. (12.6 mmole) of α-methyl-γ-morpholinobutyric acid hydrochloride, 2.78 g. (13.5 mmole) of dicyclohexylcarbodiimide and 250 ml. of methylene chloride was stirred at room temperature for 16 hours. The reaction mixture was cooled and the by-product of dicyclohexylurea was removed by suction filtration. The solvent was removed and the residue dissolved in a mixture of methylene chloride/cyclohexane and again filtered to remove a small amount of insoluble material. After evaporation of the solvents, the material was dissolved in methylene chloride and converted to the dihydrochloride salt by the addition of ethereal hydrogen chloride. The solvents were removed and the residue was recrystallized from a methylene chloride/diethyl ether mixture to give 4.2 g. (52%) of colorless crystals, m.p. 188°-192° C. The sample was shown to be free of starting material by thin layer chromatography (10% MeOH/CHCl 3), and the infrared and nuclear magnetic resonance spectra were consistent with the proposed structure.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe by-product of dicyclohexylurea was removed by suction filtration
  3. customThe solvent was removed
  4. dissolutionthe residue dissolved in a mixture of methylene chloride/cyclohexane
  5. filtrationagain filtered
  6. customto remove a small amount of insoluble material
  7. customAfter evaporation of the solvents
  8. dissolutionthe material was dissolved in methylene chloride
  9. additionconverted to the dihydrochloride salt by the addition of ethereal hydrogen chloride
  10. customThe solvents were removed
  11. customthe residue was recrystallized from a methylene chloride/diethyl ether mixture
  12. customto give 4.2 g

Sources & evidence

ORD record
ord-f344edaa0be44f6bb9d688975d392c14
Source dataset
uspto-grants-1977_08
Patent number
US04042694

Reaction notes

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