Hydrochloric Acid → HCID 70182114, compound

HRID 651340Notes

Reaction equation

HRID 651340 reaction equation
[H-].[Na+].[C:3]1([CH2:13][N:14]2[CH2:30][CH2:29][C:17]3([N:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH2:20][NH:19][C:18]3=[O:28])[CH2:16][CH2:15]2)[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1.Br[CH:32]([CH3:38])[C:33]([O:35][CH2:36][CH3:37])=[O:34].[ClH:39]>CCCCCCC.CN(C)C=O.O1CCCC1.CCOCC.C(OCC)(=O)C.O>[ClH:39].[CH2:36]([O:35][C:33](=[O:34])[CH:32]([N:19]1[C:18](=[O:28])[C:17]2([CH2:29][CH2:30][N:14]([CH2:13][C:3]3[C:12]4[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=4)[CH:6]=[CH:5][CH:4]=3)[CH2:15][CH2:16]2)[N:21]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:20]1)[CH3:38])[CH3:37]

Participants

11

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 79040Ethyl 2-bromopropionateHCID 9907463HCID 9907463, compound2×

Product 1

HCID 70182114HCID 70182114, compoundYield 85%

Reagents, catalysts & solvents 6

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

Sodium hydride, 60% (0.156 g, 3.9 mmol) was suspended in dry heptane (5 ml) and stirred under nitrogen for 5 minutes. The solvent was decanted and dry dimethyl formamide (2 ml) was added. 8Naphthalen-1-ylmethyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (1.115 g, 3.0 mmol), dissolved in dry dimethyl formamide (11 ml) was added dropwise under cooling in an ice bath. The mixture was stirred at 0° C. for 1 h. An aliquot of the resulting solution of deprotonated 1-phenyl-8-naphthalen-1-ylmethyl-1,3,8-triazaspiro[4.5]decan-4-one (2.3 ml, 0.5 mmol) was added to ethyl 2-bromopropionate and the mixture was stirred at room temperature overnight. Water (15 ml) and ethyl acetate (15 ml) were added and the mixture was shaken, the organic phase was separated and successively washed with water (2×10 ml) and brine (10 ml). The organic phase was dried over magnesium sulfate and the solvent was evaporated in vacuo. The crude product was purified by column chromatography on silica gel using a mixture of ethyl acetate and dichloromethane 1:4 to give the pure base, which was dissolved in tetrahydrofuran (3 ml) and an excess of a solution of hydrogen chloride in ether was added. Crystallization occurred on the careful addition of ether (6 ml). The precipitate was collected by filtration and dried to give the title compound (217 mg, 85% yield).

Workup

  1. customThe solvent was decanted
  2. additiondry dimethyl formamide (2 ml) was added
  3. additionwas added dropwise
  4. temperatureunder cooling in an ice bath
  5. stirringThe mixture was stirred at 0° C. for 1 h
  6. stirringthe mixture was stirred at room temperature overnight
  7. stirringthe mixture was shaken
  8. customthe organic phase was separated
  9. washsuccessively washed with water (2×10 ml) and brine (10 ml)
  10. dry with materialThe organic phase was dried over magnesium sulfate
  11. customthe solvent was evaporated in vacuo
  12. customThe crude product was purified by column chromatography on silica gel using
  13. additiona mixture of ethyl acetate and dichloromethane 1:4
  14. customto give the pure base, which
  15. customCrystallization
  16. additionoccurred on the careful addition of ether (6 ml)
  17. filtrationThe precipitate was collected by filtration
  18. customdried

Sources & evidence

ORD record
ord-0981268964f640598981dba3b909a54a
Source dataset
uspto-grants-2001_08
Patent number
US06277991B1

Reaction notes

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