Oxalyl chloride → HCID 57781142, compound

HRID 1690745Notes

Reaction equation

HRID 1690745 reaction equation
[CH3:1][C:2]1([CH3:21])[CH:11]([N:12]2[C:16]([C:17](O)=[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.C(Cl)(=O)C(Cl)=O.O[NH:29][C:30](=[NH:32])[CH3:31]>ClCCl.C(Cl)(Cl)Cl>[CH3:21][C:2]1([CH3:1])[CH:11]([N:12]2[C:16]([C:17]3[O:18][N:32]=[C:30]([CH3:31])[N:29]=3)=[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

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 19864122HCID 19864122, compoundHCID 178465666HCID 178465666, compound

Product 1

HCID 57781142HCID 57781142, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

3-(3,3-Dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carboxylic acid (0.538 g, 1.88 mmol) (Example 23) is dissolved in dichloromethane (4 mL) and cooled to 0° C. Oxalyl chloride (0.41 mL, 4.702 mmol) is added and the cooling bath is removed. The mixture is stirred at room temperature for 3 h. The reaction mixture is concentrated in vacuo. The residue obtained is redissolved in chloroform and N-hydroxyacetamidine (0.181 g, 2.44 mmol) is added. The reaction mixture is stirred at reflux for 72 h. The mixture is cooled to room temperature, washed with saturated solution of sodium bicarbonate and is extracted with dichloromethane. The organic phase is dried over Na2SO4 and concentrated in vacuo. The residue is purified by silica gel chromatography (hexane-ethyl acetate, 3:7) to give dimethyl-4-[5-(3-methyl-[1,2,4]oxadiazol-5-yl)-imidazol-1-yl]-isochroman-1-one as a white solid; MS (ESI) m/z 325.0 (M+H); 1H NMR (400 MHz, MeOD) δ ppm 1.26 (s, 3 H), 1.61 (s, 3 H), 2.55 (s, 3 H), 6.94 (s, 1 H), 7.56 (d, J=7.1 Hz, 1 H), 7.63 (s, 1 H), 7.72 (td, J=7.6, 1.3 Hz, 1 H), 7.80 (td, J=7.6, 1.3 Hz, 1 H), 8.01 (s, 1 H), 8.30 (dd, J=7.8, 1.3 Hz, 1 H).

Workup

  1. customthe cooling bath is removed
  2. concentrationThe reaction mixture is concentrated in vacuo
  3. customThe residue obtained
  4. stirringThe reaction mixture is stirred
  5. temperatureat reflux for 72 h
  6. temperatureThe mixture is cooled to room temperature
  7. washwashed with saturated solution of sodium bicarbonate
  8. extractionis extracted with dichloromethane
  9. dry with materialThe organic phase is dried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customThe residue is purified by silica gel chromatography (hexane-ethyl acetate, 3:7)

Sources & evidence

ORD record
ord-58831ee62e3b4686919aaf52c1a6aac1
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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