Hydrochloric Acid → Methyl 3-phenacyl-indole-4-carboxylate

HRID 489515Notes

Reaction equation

HRID 489515 reaction equation
[NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([O:12][CH3:13])=[O:11])[C:4]=2[CH:3]=[CH:2]1.[C:14](Cl)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Cl-].[Al+3].[Cl-].[Cl-].Cl.[OH-].[K+].Cl[CH:31](Cl)C>>[CH2:31]([C:3]1[C:4]2[C:5]([C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:7]=[CH:8][C:9]=2[NH:1][CH:2]=1)[C:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:21]

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 63651,1-DichloroethaneHCID 7412Benzoyl chlorideHCID 14797Potassium HydroxideHCID 2733668methyl 1H-indole-4-carboxylateHCID 6451240Aluminum(III) Chloride

Product 1

HCID 22266690Methyl 3-phenacyl-indole-4-carboxylate

Procedure

A solution of methyl indole-4-carboxylate (40 mg, 0.23 mmol) in dichloroethane (2 mL) was treated with benzoyl chloride (0.69 mmol) at room temperature. The orange solution was cooled with an ice/water bath and treated with aluminum chloride (0.69 mmol). The dark-orange solution was warmed to room temperature over 1 hour, then poured into ice-cold aqueous 2M HCl. The aqueous solution was adjusted to pH=9-10 with KOH (s), and extracted with CH2Cl2 (10 mL×3). The organic solution was washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product was purified by radial chromatography (1 mm silica gel; 3% MeOH in CHCl3) to give methyl 3-phenacyl-indole-4-carboxylate as an oil, 63 mg (99%). A solution of the 3-phenacyl carboxy indole (60 mg, 0.25 mmol) in MeOH (5 mL) and conc. HCl (0.1 mL) was treated with hydrazine hydrate (36 mg, 0.73 mmol) and the solution was heated at reflux for 3 h. The reaction was quenched with ice/water, and the aqueous layer was adjusted to pH=10-11 with KOH (s) and extracted with CH2Cl2 (30 mL×3). The organic solution was washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product was crystallized (CH2Cl2/hexanes) to give 1,5-dihydro-3-phenyl-[1,2]diazepino[4,5,6-cd]-indol-6-one, 33 mg (51%), as a bright-yellow solid. mp 177-179° C.; 1H NMR (300 MHz, d6-DMSO) δ 7.22 (m, 2H), 7.47 (m, 3H), 7.58 (m, 4H), 10.45 (s, 1H), 11.92 (br s, 1H); Anal. (C10H7N3O.0.75 H2O) C, H, N.

Workup

  1. temperatureThe orange solution was cooled with an ice/water bath
  2. extractionextracted with CH2Cl2 (10 mL×3)
  3. washThe organic solution was washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by radial chromatography (1 mm silica gel; 3% MeOH in CHCl3)

Sources & evidence

ORD record
ord-14ddc2affb9546eba1af020eb62b6cf9
Source dataset
uspto-grants-2005_12
Patent number
US06977298B2

Reaction notes

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