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

HRID 1474530Notes

Reaction equation

HRID 1474530 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-66ed3ec85ede429880d50c611c69c139
Source dataset
uspto-grants-2015_04
Patent number
US09018229B2

Reaction notes

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