Ethanol → 3-(3,3-dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carboxylic acid ethyl ester

HRID 1690742Notes

Reaction equation

HRID 1690742 reaction equation
[OH:1][CH2:2][C:3]1[N:7]([CH:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:18])[O:10][C:9]2([CH3:20])[CH3:19])[CH:6]=[N:5][CH:4]=1.[CH2:21]([OH:23])[CH3:22].[C-]#N.[Na+]>C1COCC1.[O-2].[O-2].[Mn+4]>[CH2:21]([O:23][C:2]([C:3]1[N:7]([CH:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:18])[O:10][C:9]2([CH3:20])[CH3:19])[CH:6]=[N:5][CH:4]=1)=[O:1])[CH3:22]

Participants

6

Reactant 3

HCID 702EthanolHCID 8929Sodium CyanideHCID 577811224-(5-Hydroxymethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one

Product 1

HCID 167527653-(3,3-dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(5-hydroxymethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one (0.56 g, 2.0 mmol) (Example 6d) in THF (10 mL) is added ethanol (0.6 mL), sodium cyanide (0.111 g, 2.26 mmol) and manganese dioxide (2.69 g, 30.9 mmol). The mixture is stirred at reflux for 2 days, filtered and concentrated in vacuo. The residue is purified by silica gel chromatography (gradient ethyl acetate in heptane, 20% to 90%) to give 3-(3,3-dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carboxylic acid ethyl ester as oil; HRMS (ESI) m/z 315.1355 [(M+H)+: Calcd for C17H18N2O4: 315.1345]; 1H NMR (400 MHz, MeOD) of the HCl salt δ ppm 1.24 (s, 3 H), 1.43 (t, J=7.1 Hz, 3 H), 1.55 (s, 3 H), 4.46 (q, J=7.1 Hz, 2 H), 6.83 (s, 1 H), 7.53 (d, J=7.6 Hz, 1 H), 7.66-7.71 (m, 2 H), 7.78 (td, 1 H), 7.91 (s, 1 H), 8.26 (dd, J=7.8, 1.3 Hz, 1 H)

Workup

  1. temperatureat reflux for 2 days
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe residue is purified by silica gel chromatography (gradient ethyl acetate in heptane, 20% to 90%)

Sources & evidence

ORD record
ord-47c7be7d82ae48e583fe0107281861b5
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

Loading…