Isopropanol → HCID 57781118, compound

HRID 1690743Notes

Reaction equation

HRID 1690743 reaction equation
[CH3:1][C:2]1([CH3:21])[CH:11]([N:12]2[C:16]([C:17]([OH:19])=[O:18])=[CH:15][N:14]=[CH:13]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:20])[O:3]1.CN(C)C=O.C(Cl)(=O)C(Cl)=O.[CH:33](O)([CH3:35])[CH3:34]>ClCCl>[CH:33]([O:18][C:17]([C:16]1[N:12]([CH:11]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4](=[O:20])[O:3][C:2]2([CH3:21])[CH3:1])[CH:13]=[N:14][CH:15]=1)=[O:19])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 19864122HCID 19864122, compound

Product 1

HCID 57781118HCID 57781118, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

3-(3,3-Dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carboxylic acid (0.075 g, 0.262 mmol) (Example 23) is dissolved in dichloromethane (2 mL). Catalytic amount of dimethylformamide (0.002 mL, 0.0262 mmol) is added to the reaction mixture and cooled to 0° C. Oxalyl chloride (0.016 mL, 0.655 mmol) is added and the cooling bath is removed. The mixture is stirred at room temperature for 2 h and concentrated in vacuo. The residue obtained is redissolved in dichloromethane, and isopropanol (10 mL) is added. The reaction mixture is stirred at room temperature for 1 h, whereupon the volatiles are removed in vacuo. Saturated aqueous sodium bicarbonate is added and extracted with dichloromethane. The combined organic phase is dried over Na2SO4 and concentrated in vacuo. The residue is purified by silica gel chromatography (hexane-ethyl acetate, 1:1) to give 3-(3,3-dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carboxylic acid isopropyl ester; MS (ESI) m/z 329.0 (M+H); 1H NMR (400 MHz, MeOD) of the HCl salt δ ppm 1.34 (s, 3 H), 1.48 (d, J=5.9 Hz, 3 H), 1.49 (d, J=5.9 Hz, 3 H), 1.62 (s, 3 H), 5.42 (sept, J=5.9 Hz, 1 H), 7.02 (s, 1 H), 7.67 (d, J=7.6 Hz, 1 H), 7.75-7.81 (m, 1 H), 7.82-7.90 (m, 1 H), 8.33 (dd, J=7.8, 1.5 Hz, 1 H), 8.38 (d, J=1.3 Hz, 1 H), 8.76 (d, J=1.0 Hz, 1 H)

Workup

  1. customthe cooling bath is removed
  2. concentrationconcentrated in vacuo
  3. customThe residue obtained
  4. stirringThe reaction mixture is stirred at room temperature for 1 h, whereupon the volatiles
  5. customare removed in vacuo
  6. additionSaturated aqueous sodium bicarbonate is added
  7. extractionextracted with dichloromethane
  8. dry with materialThe combined organic phase is dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by silica gel chromatography (hexane-ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-98ae39a0460141fea7f0599a50267a6a
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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