3-(Chloromethyl)pyridine hydrochloride → HCID 67482386, compound

3-Nitro-1H-pyrazole (prepared as in Example 15, 113 mg, 1.00 mmol) was dissolved in N,N-dimethylformamide (5 mL) and cooled in an ice bath. A 60% suspension of sodium hydride in mineral oil (88 mg, 2.2 mmol) was added in portions and the cooling bath was removed. After stirring 1.5 h, a mixture of 3-picolyl chloride hydrochloride (164 mg, 1.00 mmol) in N,N-dimethylformamide (1 mL) was added. The reaction mixture was stirred 65 h, then evaporated in vacuo. The residue was treated with saturated aqueous sodium bicarbonate solution (1 mL) and extracted with chloroform (2×3 mL). The combined organic phases were dried over sodium sulfate and evaporated in vacuo. The residue was stirred in ethyl acetate (50 mL) and filtered. The filtrate was evaporated in vacuo and the remaining material was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; (50% ethyl acetate/hexanes to 100% ethyl acetate) to afford 3-(3-nitro-pyrazol-1-ylmethyl)-pyridine (114 mg, 56%) as a clear, faintly yellow oil which began to solidify over time: LC-MS (ESI) m/e calcd for C9H8N4O2 [M+] 204.06, found 205 [M+H+].

1. temperaturecooled in an ice bath
2. customthe cooling bath was removed
3. additionwas added
4. stirringThe reaction mixture was stirred 65 h
5. customevaporated in vacuo
6. additionThe residue was treated with saturated aqueous sodium bicarbonate solution (1 mL)
7. extractionextracted with chloroform (2×3 mL)
8. dry with materialThe combined organic phases were dried over sodium sulfate
9. customevaporated in vacuo
10. stirringThe residue was stirred in ethyl acetate (50 mL)
11. filtrationfiltered
12. customThe filtrate was evaporated in vacuo
13. customthe remaining material was purified by flash column chromatography (Merck silica gel 60, 40-63 μm

ORD record

ord-6f4cf4c59cec4625947c5594a5347226

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07902248B2