Methyl iodide → Methyl (+/-)-13-cyclohexyl-6,7-dihydro-6-carbomethoxy-6-methyl-5H-indolo[2,1-a][2]benzazepine-10-carboxylate

HRID 1394899Notes

Reaction equation

HRID 1394899 reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.[C:9]([CH:13]1[CH2:19][C:18]2[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=2[C:16]2=[C:24]([CH:35]3[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)[C:25]3[CH:26]=[CH:27][C:28]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][C:30]=3[N:15]2[CH2:14]1)([O:11][CH3:12])=[O:10].IC>C1COCC1>[CH:35]1([C:24]2[C:25]3[CH:26]=[CH:27][C:28]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][C:30]=3[N:15]3[CH2:14][C:13]([C:9]([O:11][CH3:12])=[O:10])([CH3:2])[CH2:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[C:16]=23)[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 58765149dimethyl 13-cyclohexyl-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylate

Product 1

HCID 58677045Methyl (+/-)-13-cyclohexyl-6,7-dihydro-6-carbomethoxy-6-methyl-5H-indolo[2,1-a][2]benzazepine-10-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-50 °C

Procedure

A solution of LDA in THF (1.2 mL of 0.5 N, 0.60 mmol) was added to a solution of methyl (±)-6-carbomethoxy-13-cyclohexyl-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylate (160 mg, 0.37 mmol) in THF (5 mL) at −78° C. Stirring was continued at −78° C. for 15 min when the mixture was slowly warmed to −50° C. Iodomethane (35 μL, 0.56 mmol) was added and the mixture was slowly warmed to −10° C. Stirring was continued for 30 min. The solution was quenched with MeOH. The solution was extracted with ethyl acetate and the extract washed with dilute HCl (2×), brine (3×), and then dried (Na2SO4). The extract was concentrated and the crude product purified on the Shimadzu preparative liquid chromatograph. The product containing fraction was concentrated on a Speed Vac® to leave the titled compound as a white solid (140 mg, 85%). ESI-MS m/z 446 (MH+) 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 1.19-1.33 (m, 3 H) 1.31-1.52 (m, 3 H) 1.63-1.84 (m, 3 H) 1.87-2.15 (m, 4 H) 2.34 (d, J=13.73 Hz, 0.4 H) 2.70 (d, J=13.73 Hz, 0.6 H) 2.88-3.12 (m, 2 H) 3.21 (d, J=13.73 Hz, 0.4 H) 3.33 (d, J=14.65 Hz, 0.6 H) 3.75 (d, J=10.68 Hz, 3 H) 3.95 (s, 3 H) 4.34 (d, J=14.65 Hz, 0.4 H) 4.87 (d, J=14.65 Hz, 0.6 H) 7.30-7.48 (m, 4 H) 7.69-7.79 (m, 1 H) 7.82-7.92 (m, 1 H) 8.11 (s, 0.4 H) 8.22 (s, 0.6 H).

Workup

  1. temperaturethe mixture was slowly warmed to −10° C
  2. stirringStirring
  3. waitwas continued for 30 min
  4. customThe solution was quenched with MeOH
  5. extractionThe solution was extracted with ethyl acetate
  6. washthe extract washed with dilute HCl (2×), brine (3×)
  7. dry with materialdried (Na2SO4)
  8. concentrationThe extract was concentrated
  9. customthe crude product purified on the Shimadzu preparative liquid chromatograph
  10. additionThe product containing fraction
  11. concentrationwas concentrated on a Speed Vac®

Sources & evidence

ORD record
ord-910d8de538994436b38641b6ea25ef9e
Source dataset
uspto-grants-2008_03
Patent number
US07348425B2

Reaction notes

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