Hydrochloric Acid → 3-(2,2-dimethyl-2,3-dihydro-benzofuran-3-yl)-3H-imidazole-4-carboxylic acid methyl ester

HRID 2089487Notes

Reaction equation

HRID 2089487 reaction equation
[CH3:1][C:2]1([CH3:12])[CH:6](O)[C:5]2[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=2[O:3]1.[NH:13]1[CH:17]=[C:16]([C:18]([O:20][CH3:21])=[O:19])[N:15]=[CH:14]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>[CH3:21][O:20][C:18]([C:16]1[N:15]([CH:6]2[C:5]3[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=3[O:3][C:2]2([CH3:12])[CH3:1])[CH:14]=[N:13][CH:17]=1)=[O:19]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 97268Di-tert-butyl azodicarboxylateHCID 190130202,2-Dimethyl-2,3-dihydrobenzofuran-3-olHCID 178418785HCID 178418785, compound

Product 1

HCID 675481143-(2,2-dimethyl-2,3-dihydro-benzofuran-3-yl)-3H-imidazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2,2-dimethyl-2,3-dihydro-benzofuran-3-ol (375 mg, 2.28 mmol) in THF (20 mL) is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 432 mg, 3.42 mmol), followed by triphenylphosphine (896 mg, 3.42 mmol). The reaction is cooled to 0° C. and di-t-butyl azodicarboxylate (787 mg, 3.42 mmol) is added. The reaction is permitted to warm to room temperature and stirred for 2 hours. The reaction mixture is then 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 1:5) to furnish 3-(2,2-dimethyl-2,3-dihydro-benzofuran-3-yl)-3H-imidazole-4-carboxylic acid methyl ester; HRMS: (ESI) m/z 245.0934 [(M+H)+: Calcd for C13H13N2O3: 245.0926]; 1H NMR (400 MHz, CDCl3) δ ppm 1.05 (s, 3H), 1.57 (s, 3 H), 3.92 (s, 3 H), 6.32 (s, 1 H), 6.92 (d, J=8.1 Hz, 1 H), 6.95-7.02 (m, 2 H), 7.25 (s, 1 H), 7.32-7.40 (m, 1 H), 7.80 (s, 1 H).

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe reaction mixture is then 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 1:5)

Sources & evidence

ORD record
ord-a55a6e28c07d4ca69b6abae50a1cf4e6
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

Loading…