Methyl 8-bromooctanoate → 1-(7-Methoxycarbonylheptyl)-3-methyl-2-(3-pyridyl)indole

HRID 1462617Notes

Reaction equation

HRID 1462617 reaction equation
CC(C)([O-])C.[K+].[CH3:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][C:9]=1[C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1.Br[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32]>CN(C)C=O>[CH3:34][O:33][C:31]([CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][N:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8]([CH3:7])=[C:9]1[C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)=[O:32]

Participants

5

Reactant 3

HCID 11107373Methyl 8-bromooctanoateHCID 155913683-Methyl-2-(3-pyridyl)indoleHCID 23665647Potassium tert-butoxide

Product 1

HCID 133620861-(7-Methoxycarbonylheptyl)-3-methyl-2-(3-pyridyl)indole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Dimethylformamide (1640 ml) was charged into a 20 gallon glass kettle along with 430 g of potassium t-butoxide. This solution was stirred under nitrogen and cooled to -8°. A solution of 682 g of 3-methyl-2-(3-pyridyl)indole in 3280 ml of dimethylformamide was added over 0.75 hour while the temperature is maintained below 0°. After 2 hours of stirring of -10°, 1640 ml of a solution of 780 g of methyl 8-bromooctanoate in dimethylformamide was added over 1 hour. Reaction temperature was maintained below 0°. After 2 hours stirring, the reaction mixture was allowed to warm to room temperature overnight. The rust-colored mixture was then cooled to about 5° and treated with 19.7 L of ice water. The temperature rose to 25°. After 0.5 hour stirring, the mixture was extracted with 2×8 L of ether. The extracts were dried (MgSO4) and concentrated in vacuo to give the methyl ester of 1-(7-methoxycarbonylheptyl)-3-methyl-2-(3-pyridyl)indole as an oil. 1293 g of this oil was treated with 6.53 L of IN NaOH and warmed over steam to 90° for 2.5 hours. After cooling to room temperature, the solution was washed with 3×3 L of ether. The aqueous layer was cooled to 10° and acidified to pH 3.5 with 3.4 L of 2N HCl. The heavy suspension which resulted was extracted with 4×4 L of methylene chloride. The combined extracts were washed once with 4 L of water and dried (MgSO4). After filtration and evaporation of solvent in vacuo at 60°, ether (1.5 L) trituration of the residue and drying gave 1-(7-carboxyheptyl)-3-methyl-2-(3-pyridyl)indole, m.p. 113°-115°. Recrystallization from ethanol raised melting point to 114°-116°.

Workup

  1. temperaturecooled to -8°
  2. temperatureis maintained below 0°
  3. stirringAfter 2 hours of stirring of -10°
  4. customReaction temperature
  5. temperaturewas maintained below 0°
  6. stirringAfter 2 hours stirring
  7. customrose to 25°
  8. stirringAfter 0.5 hour stirring
  9. extractionthe mixture was extracted with 2×8 L of ether
  10. dry with materialThe extracts were dried (MgSO4)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d7ef1de5e34147578008f776cb4d82cc
Source dataset
uspto-grants-1984_07
Patent number
US04460777

Reaction notes

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