Sodium Nitrite → 3-(2-Fluorobenzyl)-3-(methoxymethyl)piperidin-1-amine

In an argon purged flask, 3-(2-fluorobenzyl)-3-(methoxymethyl)piperidine (337 mg, 1.23 mmol) was dissolved in water (0.8 mL) and acetic acid (2 mL). A solution of sodium nitrite (170 mg, 2.46 mmol) and water (1 mL) was drop wise added to the reaction flask. The reaction was stirred for an hour at room temperature. Water (5 mL) was added to the reaction mixture. The reaction mixture then was extracted 3 times with ethyl acetate (20 mL). The organic layers were combined, dried with sodium sulfate, and concentrated. The oil was dissolved in acetic acid (5 mL). The solution was drop-wise added to a suspension of Zn (321 mg, 4.92 mmol) in acetic acid (1 mL) and water (1 mL) solution. The reaction was stirred for 1.5 hour at room temperature. Upon completion, the reaction was filtered through celite. The Zn and salt was rinsed with 1N HCl in water. The filtrate was concentrated to yield crude hydrogen chloride salt of the amine. The crude product was progressed to the next step without further purification.

1. additionwise added to the reaction flask
2. extractionThe reaction mixture then was extracted 3 times with ethyl acetate (20 mL)
3. dry with materialdried with sodium sulfate
4. concentrationconcentrated
5. dissolutionThe oil was dissolved in acetic acid (5 mL)
6. stirringThe reaction was stirred for 1.5 hour at room temperature
7. filtrationUpon completion, the reaction was filtered through celite
8. washThe Zn and salt was rinsed with 1N HCl in water
9. concentrationThe filtrate was concentrated

ORDレコード

ord-c5b82f8f6a174ebc8ce9b09dc12a82b2

出典データセット

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09351965B2