Thionyl Chloride → 2-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine
Reaction equation
[CH2:1]([O:8][C:9]1[C:14]([CH2:15]O)=[C:13]([CH3:17])[CH:12]=[C:11]([CH3:18])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=S(Cl)[Cl:21].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:1]([O:8][C:9]1[C:14]([CH2:15][Cl:21])=[C:13]([CH3:17])[CH:12]=[C:11]([CH3:18])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Conditions
- Temperature
- -40 °C
Procedure
21.5 g×2 batches: To a solution of [2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methanol (Cpd Y, 21.5 g, 88.5 mmol) in anhydrous CH2Cl2 (400 mL) was added SOCl2 (16.0 g, 133 mmol) at −40° C. under N2. The mixture was stirred at the −40° C. for 30 minutes. The reaction mixture was poured into ice-water (300 mL) and adjusted pH 7˜8 with NaHCO3 (solid). The mixture was separated and the aqueous layer was extracted with CH2Cl2 (300 mL). The combined organic layers were washed with brine (300 mL), dried over Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc, 100:1) to give the title compound (Cpd Z, 27.5 g, 60%) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 7.51-7.49 (d, 2H), 7.41-7.37 (t, 2H), 7.34-7.30 (t, 1H), 6.62 (s, 1H), 5.45 (s, 2H), 4.73 (s, 2H), 2.42 (s, 3H), 2.37 (s, 3H). MS 261.9 [M+H].
Workup
- customThe mixture was separated
- extractionthe aqueous layer was extracted with CH2Cl2 (300 mL)
- washThe combined organic layers were washed with brine (300 mL)
- dry with materialdried over Na2SO4
- concentrationconcentrated under vacuum
- customThe residue was purified by column chromatography (petroleum ether/EtOAc, 100:1)
Sources & evidence
- ORD record
- ord-9ba25ba85a6c4aa08339cb723e785ee8
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09040515B2
Reaction notes
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