Diethyl Malonate → HCID 19603745, compound

HRID 1604685Notes

Reaction equation

HRID 1604685 reaction equation
C[Mg]Br.[C:4]([O:12][CH2:13][CH3:14])(=[O:11])[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].[C:15]([C:19]1[N:20]=[C:21]([C:24]2[O:25][C:26]3[CH:32]=[CH:31][C:30]([CH2:33][N:34]4[C:42]5[C:37](=[CH:38][C:39]([CH2:43]I)=[CH:40][CH:41]=5)[C:36]([C:45]#[N:46])=[CH:35]4)=[CH:29][C:27]=3[CH:28]=2)[S:22][CH:23]=1)([CH3:18])([CH3:17])[CH3:16]>O1CCCC1>[C:15]([C:19]1[N:20]=[C:21]([C:24]2[O:25][C:26]3[CH:32]=[CH:31][C:30]([CH2:33][N:34]4[C:42]5[C:37](=[CH:38][C:39]([CH2:43][CH:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[C:4]([O:12][CH2:13][CH3:14])=[O:11])=[CH:40][CH:41]=5)[C:36]([C:45]#[N:46])=[CH:35]4)=[CH:29][C:27]=3[CH:28]=2)[S:22][CH:23]=1)([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 19603755HCID 19603755, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 19603745HCID 19603745, compoundYield 83.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-{[2-(4-tert-butylthiazol-2-yl)benzofuran-5-yl]methyl}-5-(chloromethyl)indole-3-carbonitrile (0.65 g) and potassium iodide (0.91 g) in acetone (5 ml) was stirred at room temperature for 1 hour. The mixture was evaporated under reduced pressure and the residue was dissolved with dichloromethane. After removal of the resulting insolble mass by filtration, and the filtrate was evaporated under reduced pressure to give 1-{[2-(4-tert-butylthiazol-2-yl)benzofuran-5-yl]methyl}-5-(iodomethyl)indole-3-carbonitrile (0.88 g). Methyl magnesium bromide (1M) in tetrahydrofuran solution (15 ml) was added dropwise to diethyl malonate (5.41 g) under ice-cooling. After the mixture was stirred at room temperature for 1.5 hours, 1-{[2-(4-tert-butylthiazol-2-yl)benzofuran-5-yl]methyl}-5-(iodomethyl)indole-3-carbonitrile (0.88 g) was added to the mixture. After several hours, the resulting mixture was partitioned between diluted hydrochloric acid and ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel and eluted with a mixture of toluene and ethyl acetate. The fractions containing the objective compounds were combined and concentrated under reduced pressure to give ethyl 3-{1-{[2-(4-tert-butylthiazol-2-yl)benzofuran-5-yl]methyl}-3-cyanoindol-5-yl}-2-(ethoxycarbonyl)propionate (0.78 g).

Workup

  1. temperaturecooling
  2. waitAfter several hours
  3. customthe resulting mixture was partitioned between diluted hydrochloric acid and ethyl acetate
  4. washThe ethyl acetate layer was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated under reduced pressure
  7. washeluted with a mixture of toluene and ethyl acetate
  8. additionThe fractions containing the objective compounds
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a4b3c5d12b0a4b5e98bfaf55b6d56492
Source dataset
uspto-grants-1999_11
Patent number
US05994378

Reaction notes

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