Potassium Iodide → HCID 15104472, compound

HRID 1741901Notes

Reaction equation

HRID 1741901 reaction equation
N1C2C(=CC(C(OCC3C=CC=CC=3)=O)=CC=2)C=C1.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].[I-:34].[K+]>CN(C)C=O>[I:34][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]

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 2759828Methyl 4-(bromomethyl)-3-methoxybenzoateHCID 10264164Benzyl 1H-indole-5-carboxylate

Product 1

HCID 15104472HCID 15104472, compoundYield 26.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of benzyl indole-5-carboxylate (86.8 g), methyl 4-bromomethyl-3-methoxybenzoate (89.5 g) and potassium iodide (57.4 g) in N,N-dimethylformamide (900 mL) was heated to 80° C. for 10 hours. The reaction mixture was evaporated and partitioned between diethyl ether and water. The organic layer was separated and washed with water. The aqueous washes were combined and extracted with diethyl ether. The combined organic extract was dried (MgSO4) and evaporated. The residue was purified by flash chromatography, eluting sequentially with 0:1:1, 2:48:50, 4:46:50, 5:45:50, and 10:40:50 ethyl acetate:hexane:methylene chloride, to afford methyl 4-iodomethyl-3-methoxybenzoate (27.8 g), recovered benzyl indole-5-carboxylate (29.6 g), and the crude product as a tan solid (50.6 g). Treatment of the recovered benzyl indole-5-carboxylate (29.6 g) in N,N-dimethylformamide (250 mL) with methyl 4-iodomethyl-3-metboxybenzoate (29.8 g) at 80° C. for 12 hours, followed by evaporation, gave a dark residue, which was dissolved in diethyl ether and washed with water (3 times). The aqueous washes were combined and extracted with diethyl ether. The combined organic extract was dried (MgSO4) and evaporated. The residue was purified by flash chromatography, eluting sequentially with 0:1:1, 2:48:50, 5:45:50, and 10:40:50 ethyl acetate:hexane:methylene chloride, to give further crude product as a tan solid (31.9 g). The combined crude product (82.5 g) was suspended in diethyl ether (400 mL), heated to reflux for 30 min, cooled and filtered to obtain methyl 4-(5-benzyloxycarbonylindol-3-ylmethyl)-3-methoxybenzoate as an ivory solid (46.1 g, 31%); partial NMR (250 MHz, CDCl3): 3.84 (s, 3H, CO2CH3), 3.88 (s, 3H, OCH3), 4.14 (s, 2H, CH2), 5.35 (s, 2H, OCH2), 6.97 (d, 1H, indole-H(2)), 8.15 (br, 1 H, NH), 8.37 (s, 1H, indole-H(4)).

Workup

  1. customThe reaction mixture was evaporated
  2. custompartitioned between diethyl ether and water
  3. customThe organic layer was separated
  4. washwashed with water
  5. extractionextracted with diethyl ether
  6. extractionThe combined organic extract
  7. dry with materialwas dried (MgSO4)
  8. customevaporated
  9. customThe residue was purified by flash chromatography
  10. washeluting sequentially with 0:1:1, 2:48:50, 4:46:50, 5:45:50, and 10:40:50 ethyl acetate

Sources & evidence

ORD record
ord-5ab680cbbd034012a0545b42721d2620
Source dataset
uspto-grants-1994_08
Patent number
US05334765

Reaction notes

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