Sodium hydride → HCID 19870592, compound

HRID 330155Notes

Reaction equation

HRID 330155 reaction equation
[H-].[Na+].[CH2:3]([NH:6][C:7](=[O:19])/[CH:8]=[CH:9]/[C:10]1[CH:18]=[C:17]2[C:13]([CH:14]=[CH:15][NH:16]2)=[CH:12][CH:11]=1)[CH2:4][CH3:5].Br[CH2:21][C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][C:23]=1[O:32][CH3:33]>CN(C)C=O>[CH2:3]([NH:6][C:7](/[CH:8]=[CH:9]/[C:10]1[CH:18]=[C:17]2[C:13]([CH:14]=[CH:15][N:16]2[CH2:21][C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][C:23]=2[O:32][CH3:33])=[CH:12][CH:11]=1)=[O:19])[CH2:4][CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2759828Methyl 4-(bromomethyl)-3-methoxybenzoateHCID 67834777HCID 67834777, compound

Product 1

HCID 19870592HCID 19870592, compoundYield 62.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (0.12 g of a 60% dispersion in mineral oil) was added to a stirred solution of E-N-propylindole-6-acrylamide (0.7 g) in N,N-dimethylformamide (35 ml) cooled by an ice bath. After approximately 1 hr, a solution of methyl 4-bromomethyl-3-methoxybenzoate (0.79 g) (see Example 1, part 1) in N,N-dimethylformamide (2 ml) was added, the cooling bath removed and the mixture stirred for 1 hr. The mixture was poured into ice and extracted with ethyl acetate. The extracts were washed with brine, dried (MgSO4) and evaporated. The residue was crystallized from a mixture of ethyl acetate and hexane to give methyl E-4-[6-[2-(propylcarbamoyl)vinyl]indol-1-ylmethyl]-3-methoxybenzoate (0.78 g) as a white solid. The mother liquor was evaporated and the residue was purified by flash chromatography, eluting with 1:1 ethyl acetate:hexane, to give a further quantity of the product (0.23 g, 84% combined yield); partial NMR (250 MHz, DMSO-d6): 0.87(t, 3H, CH2CH2CH3), 1.45(m, 2H, CH2CH2CH3), 3.12(m, 2H, CH2CH2CH3) 3.83(s, 3H, OCH3), 3.96(s, 3H, OCH3), 5.46(s, 2H, NCH2Ar), 7.98(br t, 1H, NHCO).

Workup

  1. temperaturecooled by an ice bath
  2. customthe cooling bath removed
  3. additionThe mixture was poured into ice
  4. extractionextracted with ethyl acetate
  5. washThe extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue was crystallized from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-94806823cf9c4bcda67e839d2fa1805d
Source dataset
uspto-grants-1990_01
Patent number
US04894386

Reaction notes

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