Tetrabutylammonium Hydroxide → 13-cyclohexyl-10-methoxycarbonyl-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid

HRID 2111650Notes

Reaction equation

HRID 2111650 reaction equation
[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH:19]1([C:25]2[C:26]3[CH:27]=[CH:28][C:29]([C:47]([O:49][CH3:50])=[O:48])=[CH:30][C:31]=3[N:32]3[CH2:38][C:37]([C:39]([O:41]C)=[O:40])=[CH:36][C:35]4[CH:43]=[CH:44][CH:45]=[CH:46][C:34]=4[C:33]=23)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>C1COCC1>[CH:19]1([C:25]2[C:26]3[CH:27]=[CH:28][C:29]([C:47]([O:49][CH3:50])=[O:48])=[CH:30][C:31]=3[N:32]3[CH2:38][C:37]([C:39]([OH:41])=[O:40])=[CH:36][C:35]4[CH:43]=[CH:44][CH:45]=[CH:46][C:34]=4[C:33]=23)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1

Participants

4

Reactant 2

HCID 2723671Tetrabutylammonium HydroxideHCID 11640545dimethyl 13-cyclohexyl-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylate

Product 1

HCID 1607274513-cyclohexyl-10-methoxycarbonyl-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammoniumhydroxide (9.1 mL, 40% solution in water) was added dropwise to a cooled solution (0° C., ice bath) containing dimethyl 13-cyclohexyl-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylate and THF (463 mL). The solution was maintained with continued cooling for 50 min. and then concentrated to a volume of about 50 mL. The resultant solution was diluted with ethyl acetate (250 mL), washed with aq. HCl (0.5 N, 3×150 mL), washed with brine (150 mL), dried (magnesium sulfate), filtered, and concentrated to afford a yellow solid. LCMS: retention time: 1.698 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 5% CH3CN/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% CH3CN/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode: m/z 416 (MH+). 1H NMR (300 MHz, DMSO-D6) δ ppm: 12.97 (s, 1H), 8.17 (m, 1H), 7.91 (m, 2H), 7.63 (m, 5H), 5.56 (s, 1H), 4.51 (m, 1H), 3.89 (m, 3H), 2.80 (m, 1H), 1.99 (m, 6H), 1.30 (m, 4H).

Workup

  1. temperatureThe solution was maintained
  2. temperaturewith continued cooling for 50 min.
  3. concentrationconcentrated to a volume of about 50 mL
  4. additionThe resultant solution was diluted with ethyl acetate (250 mL)
  5. washwashed with aq. HCl (0.5 N, 3×150 mL)
  6. washwashed with brine (150 mL)
  7. dry with materialdried (magnesium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford a yellow solid
  11. washThe elution conditions
  12. customa gradient time of 4 min
  13. customa hold time of 1 min
  14. customan analysis time of 5 min where solvent A was 5% CH3CN/95% H2O/10 mM ammonium acetate and solvent B

Sources & evidence

ORD record
ord-13e64e6f7a2b406d89c464f8f6fd61c6
Source dataset
uspto-grants-2009_04
Patent number
US07521443B2

Reaction notes

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