2-methyl-2,3,4,5-tetrahydro-1H-pyrido(4,3-b)indole → 6-(2-Methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)hexanoic acid methyl ester

HRID 403631Notes

Reaction equation

HRID 403631 reaction equation
[CH3:1][N:2]1[CH2:14][CH2:13][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=3[C:4]=2[CH2:3]1.CC(C)([O-])C.[K+].[CH3:21][O:22][C:23](=[O:30])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]Br>CN(C=O)C.C(OCC)(=O)C.O.[I-].[K+]>[CH3:21][O:22][C:23](=[O:30])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][N:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=2[C:4]2[CH2:3][N:2]([CH3:1])[CH2:14][CH2:13][C:5]1=2

Participants

8

Reactant 3

HCID 974242-methyl-2,3,4,5-tetrahydro-1H-pyrido(4,3-b)indoleHCID 4170292Methyl 6-BromohexanoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 683803066-(2-Methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)hexanoic acid methyl esterYield 41.2%

Reagents, catalysts & solvents 4

HCID 4875Potassium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (17) (0.50 g, 2.7 mmol) was placed under argon and dissolved in 5 mL of anhydrous DMF. Potassium tert-butoxide (0.32 g, 2.8 mmol) was dissolved in 3 mL of anhydrous DMF and added slowly to the reaction at room temperature. The reaction turned from orange to dark brown. After 15 min, 6-bromohexanoic acid methyl ester (0.56 g, 2.7 mmol) and 5 mg of potassium iodide were added to the reaction at room temperature. The reaction was heated to 80° C. for 2 h upon which a precipitate formed and the reaction turned from dark brown to dark orange. The reaction was then diluted with 30 mL of ethyl acetate and 30 mL of water. The organic layer was isolated and the aqueous layer extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water (2×20 mL), brine (15 mL), dried (Na2SO4) and concentrated in vacuo. Purification by MPCC (0-80% gradient of ethyl acetate in hexane) afforded the title compound (0.35 g, 40%) as a yellow oil. 1H NMR (400 MHz, DMSO): δ 7.46 (m, 2H), 7.17 (m, 1H), 7.06 (m, 1H), 4.46 (m, 2H), 4.10 (t, 2H, J=7.0 Hz), 3.66 (m, 2H), 3.56 (s, 3H), 3.16 (m, 2H), 3.00 (s, 3H), 2.28 (t, 2H, J=7.4 Hz), 1.66 (m, 2H), 1.55 (m, 2H), 1.29 (m, 2H). 13C NMR (100 MHz, DMSO): δ 173.7, 136.7, 131.3, 124.7, 121.9, 119.7, 118.0, 110.3, 101.8, 51.6, 51.0, 50.5, 42.9, 42.2, 33.6, 29.8, 26.1, 24.6, 19.8. ESI-HRMS (m/z): [M+H]+ calcd. for C19H26N2O2, 315.1959. found, 315.1945.

Workup

  1. additionadded slowly to the reaction at room temperature
  2. customformed
  3. customThe organic layer was isolated
  4. extractionthe aqueous layer extracted with ethyl acetate (2×10 mL)
  5. washThe combined organic layers were washed with water (2×20 mL), brine (15 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customPurification by MPCC (0-80% gradient of ethyl acetate in hexane)

Sources & evidence

ORD record
ord-f5bc751976224a898e32a6a98f8ab020
Source dataset
uspto-grants-2014_06
Patent number
US08748451B2

Reaction notes

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