Thionyl Chloride → 4-(5-Chloromethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one
Reaction equation
O[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.S(Cl)([Cl:23])=O>>[Cl:23][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]=1Participants
Procedure
A solution of 4-(5-hydroxymethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one (0.300 g, 1.1 mmol) (Example 6d) in thionyl chloride (3 mL) is refluxed overnight. The volatiles are removed in vacuo to give 4-(5-chloromethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one, which is redissolved in methanol (10 mL). The solution is injected in an H-Cube™ using a Pd on carbon cartridge at 0.5 mL/min, 100 bar H2 and 50° C. The solution eluting from the cartridge is collected and concentrated in vacuo. The residue is purified by semi-preparative reverse phase HPLC to give 3,3-dimethyl-4-(5-methyl-imidazol-1-yl)-isochroman-1-one as a white solid; MS (ESI) m/z 257.0 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 1.34 (s, 3 H), 1.58 (s, 3 H), 2.38 (br. s, 3 H), 5.18 (br. s, 1 H), 6.92 (s, 1 H), 7.17 (br. s, 1 H), 7.35 (br. s, 1 H), 7.58 (t, J=7.6 Hz, 1 H), 7.62-7.68 (m, 1 H), 8.26 (d, J=7.8 Hz, 1 H).
Workup
- customThe volatiles are removed in vacuo
Sources & evidence
- ORD record
- ord-abe0f183b3ff4bfeb999a55f53ea663e
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08153674B2
Reaction notes
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