Pyridine → tert-Butyl (6-(chloromethyl)pyridin-2-yl)carbamate
Reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14]O)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.O=S(Cl)[Cl:25]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][Cl:25])[N:9]=1)([CH3:4])([CH3:3])[CH3:2]Participants
Procedure
To a solution of ethyl 6-[(tert-butoxycarbonyl)amino]pyridine-2-carboxylate (456 mg, 1.71 mmol) in anhydrous ethanol (20 ml) was added pulverized CaCl2 (395 mg, 3.42 mmol). The suspension was stirred and cooled to 0° C. and NaBH4 (325 mg, 8.55 mmol) was added slowly. The reaction was stirred at 0° C. for 2 h, quenched with water, and extracted with CHCl3 (×3). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (30→50% ethyl acetate in hexane) to yield a colorless syrup (308 mg) as a mixture containing tert-butyl[6-(hydroxymethyl)pyridin-2-yl]carbamate as the major component (˜4:1 ratio). To a solution of the above mixture in CH2Cl2 (10 ml) was added pyridine (144 μl, 1.79 mmol) and SOCl2 (120 μl, 1.65 mmol). The reaction was stirred at room temperature for 4 h, quenched with water and saturated Na2CO3, and extracted with CHCl3. The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (10% ethyl acetate in hexane) to yield the title compound as a colorless syrup (208 mg, 50% over 2 steps).
Workup
- customquenched with water and saturated Na2CO3
- extractionextracted with CHCl3
- dry with materialThe combined organic layer was dried over Na2SO4
- concentrationconcentrated
- customThe residue was purified by column chromatography on silica gel (10% ethyl acetate in hexane)
Sources & evidence
- ORD record
- ord-c393f26c93b8466798fdd6b4611b5db6
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08450367B2
Reaction notes
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