Hydrochloric Acid → methyl 13-cyclohexyl-7H-indolo[2,1-a][2]benzazepine-10-carboxylate

HRID 860723Notes

Reaction equation

HRID 860723 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:29]([O:31][CH3:32])=[O:30])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19](C(OC)=O)=[CH:18][C:17]4[CH:25]=[CH:26][CH:27]=[CH:28][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-].Cl>CN(C=O)C>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:29]([O:31][CH3:32])=[O:30])=[CH:12][C:13]=3[N:14]3[CH2:20][CH:19]=[CH:18][C:17]4[CH:25]=[CH:26][CH:27]=[CH:28][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 11640545dimethyl 13-cyclohexyl-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylate

Product 1

HCID 11667856methyl 13-cyclohexyl-7H-indolo[2,1-a][2]benzazepine-10-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of dimethyl 13-cyclohexyl-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylate (2.6 g, 6.1 mmol) in DMF (60 mL) was added LiOH (1.45 g, 60 mmol) and the reaction mixture was heated at 60° C. for 2d. The reaction mixture was cooled internally with ice, acidified with 1M aqueous HCl (pH<2) and extracted with EtOAc (350 mL). The organics were washed with H2O (˜150 mL), brine (˜150 mL), dried (MgSO4), filtered and concentrated. The solids were triturated with Et2O/hexanes (1:2) and collected to yield methyl 13-cyclohexyl-7H-indolo[2,1-a][2]benzazepine-10-carboxylate, 6-carboxylic acid (2.06 g, 4.96 mmol. 81%) as a fluffy yellow solid. 1HNMR (500 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.94 (d, J=8.5 Hz, 2H), 7.88 (s, 1H), 7.88 (d, J=7.6 Hz, 1H), 7.67–7.55 (m, 4H), 5.58 (br s, 1H), 4.15 (br s, 1H), 3.90 (s, 3H), 2.84–2.75 (m, 1H), 2.10–1.65 (m, 6H), 1.49–1.07 (m, 4H). LCMS: m/e 416 (M+H)+, ret time 1.47 min, column A, 2 minute gradient.

Workup

  1. temperatureThe reaction mixture was cooled internally with ice
  2. extractionextracted with EtOAc (350 mL)
  3. washThe organics were washed with H2O (˜150 mL), brine (˜150 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe solids were triturated with Et2O/hexanes (1:2)
  8. customcollected

Sources & evidence

ORD record
ord-713802c35009491b8dc00b9f21e6f4cb
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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