Dimethylformamide → 6-(3-Chloropropyl)-8-(4-methoxyphenyl)-5-propoxy-1,2,3,6-tetrahydro-6-aza-cyclopenta[a]naphthalen-9-one

HRID 68142Notes

Reaction equation

HRID 68142 reaction equation
CN(C=O)C.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:23](=[O:24])[C:22]3[C:17](=[C:18]([O:28][CH2:29][CH2:30][CH3:31])[CH:19]=[C:20]4[CH2:27][CH2:26][CH2:25][C:21]4=3)[NH:16][CH:15]=2)=[CH:10][CH:9]=1.[H-].[Na+].Br[CH2:35][CH2:36][CH2:37][Cl:38]>C(OCC)(=O)C.O>[Cl:38][CH2:37][CH2:36][CH2:35][N:16]1[CH:15]=[C:14]([C:11]2[CH:10]=[CH:9][C:8]([O:7][CH3:6])=[CH:13][CH:12]=2)[C:23](=[O:24])[C:22]2[C:17]1=[C:18]([O:28][CH2:29][CH2:30][CH3:31])[CH:19]=[C:20]1[CH2:27][CH2:26][CH2:25][C:21]1=2

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 584925468-(4-Methoxyphenyl)-5-propoxy-1,2,3,6-tetrahydro-6-aza-cyclopenta[a]naphthalen-9-one

Product 1

HCID 584923966-(3-Chloropropyl)-8-(4-methoxyphenyl)-5-propoxy-1,2,3,6-tetrahydro-6-aza-cyclopenta[a]naphthalen-9-oneYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a DMF solution (6 ml) of 8-(4-methoxyphenyl)-5-propoxy-1,2,3,6-tetrahydro-6-aza-cyclopenta[a]naphthalen-9-one (1.26 g, 3.60 mmol) was added sodium hydride (60% oil base, 189 mg, 4.33 mmol). The mixture was stirred at room temperature for 10 minutes. To the resulting mixture was added 1-bromo-3-chloropropane (1.70 g, 10.8 mmol), followed by stirring at room temperature for 16 hours. Water and ethyl acetate were added to the reaction mixture and the resulting reaction mixture was then subjected to separation. The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice. After being dried over anhydrous sodium sulfate, the organic layer was concentrated under reduced pressure. The residue was purified using silica gel column chromatography (dichloromethane:ethyl acetate=20:1→12:1). The purified product was concentrated under reduced pressure, giving a yellow oily substance of 6-(3-chloropropyl)-8-(4-methoxyphenyl)-5-propoxy-1,2,3,6-tetrahydro-6-aza-cyclopenta[a]naphthalen-9-one (365 mg, yield: 92%).

Workup

  1. stirringby stirring at room temperature for 16 hours
  2. customthe resulting reaction mixture
  3. customwas then subjected to separation
  4. washThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice
  5. dry with materialAfter being dried over anhydrous sodium sulfate
  6. concentrationthe organic layer was concentrated under reduced pressure
  7. customThe residue was purified
  8. concentrationThe purified product was concentrated under reduced pressure

Sources & evidence

ORD record
ord-1f45af7a2e724e87b2c1e7d43b483cb2
Source dataset
uspto-grants-2014_09
Patent number
USRE045108E1

Reaction notes

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