2-methyl-2,3,4,5-tetrahydro-1H-pyrido(4,3-b)indole → Methyl 4-((2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate

HRID 403634Notes

Reaction equation

HRID 403634 reaction equation
CC(C)([O-])C.[K+].[CH3:7][N:8]1[CH2:20][CH2:19][C:11]2[NH:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=3[C:10]=2[CH2:9]1.[CH3:21][O:22][C:23](=[O:32])[C:24]1[CH:29]=[CH:28][C:27]([CH2:30]Br)=[CH:26][CH:25]=1>CN(C=O)C.[I-].[K+]>[CH3:21][O:22][C:23](=[O:32])[C:24]1[CH:29]=[CH:28][C:27]([CH2:30][N:12]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=3[C:10]3[CH2:9][N:8]([CH3:7])[CH2:20][CH2:19][C:11]2=3)=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 974242-methyl-2,3,4,5-tetrahydro-1H-pyrido(4,3-b)indoleHCID 256687Methyl 4-(bromomethyl)benzoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 68380216Methyl 4-((2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoateYield 62.8%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 6228DimethylformamideSolvent3×

Conditions

Temperature
80 °C

Procedure

Potassium tert-butoxide (0.95 g, 8.5 mmol) was placed under argon and suspended in 1 mL of anhydrous DMF. To it was added 2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (17) (1.5 g, 8.1 mmol) dissolved in 3 mL of DMF upon which the reaction turned a deep orange in color. The reaction was stirred at room temperature for 15 min after which 4-bromomethyl-benzoic acid methyl ester (1.8 g, 8.1 mmol) was added in 1 mL of DMF along with approximately 5 mg of potassium iodide. The reaction then turned a light orange in color. The reaction was stirred at 80° C. for two hours after which the reaction was quenched by the addition of 15 mL of water. The pH was adjusted to approximately 12 with 2N NaOH and the organic products were extracted with ethyl acetate (3×15 mL). The combined organic layers were washed with water (15 mL), brine (15 mL), dried with anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography (0-80% gradient of ethyl acetate in hexane) afforded the title compound (1.7 g, 61%) as a yellow oil. 1H NMR (400 MHz, CD3OD): δ 7.83 (d, 2H, J=8.3 Hz), 7.33 (d, 1H, J=7.8 Hz), 7.23 (m, 3H), 7.07 (m, 1H), 6.97 (m, 1H), 4.59 (s, 2H), 4.01 (s, 2H), 3.82 (s, 3H), 2.90 (t, 2H, J=5.5 Hz), 2.84 (t, 2H, J=5.3 Hz), 2.48 (s, 3H). 13C NMR (100 MHz, MeOD): δ 167.1, 147.5, 134.9, 130.4, 129.2, 128.1, 128.0, 127.4, 120.4, 119.2, 177.7, 108.3, 108.1, 65.4, 51.0, 50.0, 40.2, 29.2, 20.3. ESI-MS (m/z): [M+H]+ 335.2 m/z.

Workup

  1. customThe reaction
  2. customwas quenched by the addition of 15 mL of water
  3. extractionthe organic products were extracted with ethyl acetate (3×15 mL)
  4. washThe combined organic layers were washed with water (15 mL), brine (15 mL)
  5. dry with materialdried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography (0-80% gradient of ethyl acetate in hexane)

Sources & evidence

ORD record
ord-a665c3f93a634057860bc4b2da571cd9
Source dataset
uspto-grants-2014_06
Patent number
US08748451B2

Reaction notes

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