Methyl 3-(3-methyl-1-{3-(phenyl)propyl}-1H-indol-6-yl)-3-nitromethyl-propionate → 4-[3-methyl-1-(3-phenyl-propyl)-1H-indole-6-yl]-pyrrolidine-2-one

HRID 392194Notes

Reaction equation

HRID 392194 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]([CH2:17][N+:18]([O-])=O)[CH2:12][C:13](OC)=[O:14])=[CH:8][CH:9]=2)[N:4]([CH2:21][CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:3]=1.[H][H]>CO.[Ni]>[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]3[CH2:17][NH:18][C:13](=[O:14])[CH2:12]3)=[CH:8][CH:9]=2)[N:4]([CH2:21][CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:3]=1

Participants

5

Reactant 2

HCID 22663435Methyl 3-(3-methyl-1-{3-(phenyl)propyl}-1H-indol-6-yl)-3-nitromethyl-propionateHCID 178418361HCID 178418361, compound

Product 1

HCID 226634514-[3-methyl-1-(3-phenyl-propyl)-1H-indole-6-yl]-pyrrolidine-2-oneYield 79.4%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

A solution of methyl 3-(3-methyl-1-{3-(phenyl)propyl}-1H-indol-6-yl)-3-nitromethyl-propionate (0.296 g, Reference Example 38) in methanol (100 ml), under argon, was treated with excess Raney® nickel. The argon atmosphere was replaced by hydrogen at 1 atmosphere then the mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered through celite. The filtrate was evaporated and the residual crude methyl 3-(3-methyl-1-{3-(phenyl)propyl}-1H-indol-6-yl)-3-aminomethyl-propionate was dissolved in sodium hydroxide solution (15 ml, 1N). After stirring at room temperature for 1 hour the reaction mixture was extracted three times with ethyl acetate (15 ml). The combined extracts were dried over sodium sulphate then evaporated. The residue was subjected to preparative layer chromatography on silica using a mixture of ethyl acetate and hexane (1:1, v/v) as eluent to yield the title compound (0.198 g) as an oil. NMR (CDCl3): δ 2.05-2.15(m); 2.30(s); 2.55-2.60(m); 2.65-2.70(m); 2.85-2.95(m); 3.30-3.40(m); 3.60-3.70(m); 3.90-4.00(m); 4.40-4.60(m); 6.80-7.40(m). M+332.1941.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. customThe filtrate was evaporated
  3. dissolutionthe residual crude methyl 3-(3-methyl-1-{3-(phenyl)propyl}-1H-indol-6-yl)-3-aminomethyl-propionate was dissolved in sodium hydroxide solution (15 ml, 1N)
  4. stirringAfter stirring at room temperature for 1 hour the reaction mixture
  5. extractionwas extracted three times with ethyl acetate (15 ml)
  6. dry with materialThe combined extracts were dried over sodium sulphate
  7. customthen evaporated
  8. additiona mixture of ethyl acetate and hexane (1:1

Sources & evidence

ORD record
ord-c61fbdb73e394e5ea36cf3f4eda810d2
Source dataset
uspto-grants-2004_10
Patent number
US06800645B1

Reaction notes

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