Hydrochloric Acid → 5,5-Dimethyl-10-[2-methyl-4-(piperidino)butyryloxy]-8-(4-fluorophenyl-1-methylbutyl)-2-(2-propynyl)-1,2,3,4-tetrahydro-5H[1]benzopyrano[3,4-d]pyridine hydrochloride

HRID 2398867Notes

Reaction equation

HRID 2398867 reaction equation
[CH3:1][C:2]1([CH3:32])[C:24]2[CH2:25][CH2:26][N:27]([CH2:29][C:30]#[CH:31])[CH2:28][C:23]=2[C:5]2[C:6]([OH:22])=[CH:7][C:8]([C:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)([CH3:14])[CH2:11][CH2:12][CH3:13])=[CH:9][C:4]=2[O:3]1.[ClH:33].[CH3:34][CH:35]([CH2:39][CH2:40][N:41]1[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1)[C:36](O)=[O:37].C1(N=C=NC2CCCCC2)CCCCC1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.Cl>C(Cl)Cl.C1CCCCC1.C(Cl)Cl.C(OCC)C.C(OCC)C.C(Cl)Cl>[ClH:33].[CH3:32][C:2]1([CH3:1])[C:24]2[CH2:25][CH2:26][N:27]([CH2:29][C:30]#[CH:31])[CH2:28][C:23]=2[C:5]2[C:6]([O:22][C:36](=[O:37])[CH:35]([CH3:34])[CH2:39][CH2:40][N:41]3[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]3)=[CH:7][C:8]([C:10]([C:15]3[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=3)([CH3:14])[CH2:11][CH2:12][CH3:13])=[CH:9][C:4]=2[O:3]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 10868DicyclohexylcarbodiimideHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 211526892-Methyl-4-piperidin-1-yl-butyric acid hydrochlorideHCID 538194395,5dimethyl-10-hydroxy-8-(4-fluorophenyl-1-methylbutyl)-2(2-propynyl)-1,2,3,4-tetrahydro-5H[1]benzopyrano[3,4-d]pyridine

Product 1

HCID 888089095,5-Dimethyl-10-[2-methyl-4-(piperidino)butyryloxy]-8-(4-fluorophenyl-1-methylbutyl)-2-(2-propynyl)-1,2,3,4-tetrahydro-5H[1]benzopyrano[3,4-d]pyridine hydrochloride

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 21881112Ethyl ether methylene chlorideSolventHCID 21916607Dichloromethane cyclohexaneSolvent

Procedure

2.0 g. (5.05 mm.) of 5,5-dimethyl-10-hydroxy-8-(4-fluorophenyl-1-methylbutyl)-2-(2-propynyl)-1,2,3,4-tetrahydro-5H[1]benzopyrano[3,4-d]pyridine are combined with 1.12 g. (5.05 mm.) of α-methyl-γ-piperidino butyric acid hydrochloride and 1.08 g. (5.25 mm.) of dicyclohexylcarbodiimide in 110 ml. of methylene chloride and the mixture is stirred at room temperature for 16 hours. After cooling for 4 hours, the by-product of dicyclohexylurea is removed by suction filtration. The mother liquor is evaporated to give a colorless foamy residue which is dissolved in a methylene chloride/cyclohexane mixture and stored for 16 hours in the cold. A small amount of solid is separated by gravity filtration, and the solvents are removed using a rotary evaporator. The residue is dried to give a colorless solid which is dissolved in a mixture of methylene chloride/diethyl ether and converted to the dihydrochloride by the addition of a solution of hydrogen chloride is diethyl ether. The solvents are decanted, and the gummy residue crystallized upon trituration with diethyl ether. The solid is filtered and recrystallized from 20 ml. of methylene chloride/20 ml. diethyl ether to give the desired product.

Workup

  1. temperatureAfter cooling for 4 hours
  2. customthe by-product of dicyclohexylurea is removed by suction filtration
  3. customThe mother liquor is evaporated
  4. customto give a colorless foamy residue which
  5. customA small amount of solid is separated by gravity filtration
  6. customthe solvents are removed
  7. customa rotary evaporator
  8. customThe residue is dried
  9. customto give a colorless solid which
  10. customThe solvents are decanted
  11. customthe gummy residue crystallized upon trituration with diethyl ether
  12. filtrationThe solid is filtered
  13. customrecrystallized from 20 ml

Sources & evidence

ORD record
ord-0281ea2529af433292dff27f5945434d
Source dataset
uspto-grants-1977_05
Patent number
US04025630

Reaction notes

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