Hydrochloric Acid → 1-(2,2-Dimethyl-3-oxoindan-1-yl)-5-imidazolecarboxylic acid methyl ester

HRID 2089508Notes

Reaction equation

HRID 2089508 reaction equation
O[CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[C:3]1([CH3:13])[CH3:12].[NH:14]1[CH:18]=[C:17]([C:19]([O:21][CH3:22])=[O:20])[N:16]=[CH:15]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.Cl.O1CCOCC1>C1COCC1>[CH3:22][O:21][C:19]([C:17]1[N:16]([CH:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4](=[O:11])[C:3]2([CH3:13])[CH3:12])[CH:15]=[N:14][CH:18]=1)=[O:20]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 97268Di-tert-butyl azodicarboxylateHCID 13023681HCID 13023681, compoundHCID 178418785HCID 178418785, compound

Product 1

HCID 539208951-(2,2-Dimethyl-3-oxoindan-1-yl)-5-imidazolecarboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-hydroxy-2,2-dimethyl-indan-1-one (2.0 g, 11.3 mmol) in THF (50 mL) is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 1.72 g, 13.6 mmol), and triphenylphosphine (3.56 g, 13.6 mmol). The reaction is cooled to 0° C. and di-t-butyl azodicarboxylate (3.13 g, 13.6 mmol) is added. The reaction is placed at room temperature and permitted to stir for three hours. The reaction mixture is cooled to 0° C. and quenched with 4 N HCl in dioxane (5 mL, 20 mmol) and stirred for 30 minutes. The reaction is concentrated to near dryness and diluted with ethyl acetate. The organic layer is extracted three times with 1 N aqueous HCl. The aqueous extracts are combined, neutralized with Na2CO3, and extracted three times with ethyl acetate. The combined organic layers are dried with Na2SO4 filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 3:7) to furnish 3-(2,2-dimethyl-3-oxo-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; HRMS: (ESI) m/z 285.1246 [(M+H)+: Calcd for C16H16N2O3: 285.1239]; 1H NMR (400 MHz, CDCl3) δ ppm 0.82 (s, 3 H), 1.46 (s, 3 H), 4.02 (s, 3 H), 6.70 (s, 1 H), 7.39 (s, 1 H), 7.47-7.52 (m, 1 H), 7.72 (t, J=7.45 Hz, 1 H), 7.79-7.86 (m, 1 H), 7.93-7.99 (m, 2 H).

Workup

  1. customis placed at room temperature
  2. temperatureThe reaction mixture is cooled to 0° C.
  3. stirringstirred for 30 minutes
  4. concentrationThe reaction is concentrated
  5. additiondiluted with ethyl acetate
  6. extractionThe organic layer is extracted three times with 1 N aqueous HCl
  7. extractionextracted three times with ethyl acetate
  8. dry with materialThe combined organic layers are dried with Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 3:7)

Sources & evidence

ORD record
ord-60d8b1d68ed4491ba8d9c130d3901fa7
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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