Indole → HCID 59802492, compound

HRID 1672140Notes

Reaction equation

HRID 1672140 reaction equation
[Cl:1][C:2]1[C:3]([C:11]([OH:13])=[O:12])=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[C:14]1(=O)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.N1C2C(=CC=CC=2)C=C1.C[O-].[Na+]>CO>[Cl:1][C:2]1[C:3]([C:11]([OH:13])=[O:12])=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[C:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]=1

Participants

6

Reactant 4

HCID 798IndoleHCID 7967CyclohexanoneHCID 10942334Sodium MethoxideHCID 21133924HCID 21133924, compound

Product 1

HCID 59802492HCID 59802492, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a one liter round bottom flask equipped with a reflux condenser was added 26.3 grams (0.135 mol) of 7-chloro-1H-indole-6-carboxylic acid and 200 mL of dry methanol. Three equivalents (41.8 mL, 0.404 mol) of cyclohexanone was added in one portion. The heterogeneous mixture was heated to 60° C. at which point all of the indole went into solution. 6.1 equivalents of a methanolic sodium methoxide solution (0.820 mol, 187 mL) was then added in two portions. The solution was heated at reflux overnight. In the morning, the reaction mixture was cooled and evaporated to dryness. The crude mixture was diluted with 75 mL of ethyl acetate and acidified with 1M HCl. The resulting solid was filtered, washed with cold ethyl acetate and dried overnight in a vacuum desiccator to yield 32.8 grams (88%) of a powder. 1H NMR (300 MHz, CD3OD) δ 7.73 (d, J=8.42 Hz, 1H), 7.61 (d, J=8.42 Hz, 1H), 7.37 (s, 1H), 6.16 (br s, 1H), 2.42 (m, 2H), 2.24 (m, 2H), 1.79 (m, 2H), 1.68 (m, 2H), MS m/z 276.01 (M+H).

Workup

  1. customTo a one liter round bottom flask equipped with a reflux condenser
  2. temperatureThe solution was heated
  3. temperatureat reflux overnight
  4. temperatureIn the morning, the reaction mixture was cooled
  5. customevaporated to dryness
  6. additionThe crude mixture was diluted with 75 mL of ethyl acetate
  7. filtrationThe resulting solid was filtered
  8. washwashed with cold ethyl acetate
  9. customdried overnight in a vacuum desiccator

Sources & evidence

ORD record
ord-14c9265f33d443e3b4f3949d92c2246b
Source dataset
uspto-grants-2011_08
Patent number
US07998951B2

Reaction notes

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