Sodium Azide → trans-3-Azidomethyl-1-[2-(4-fluorophenyl)-ethyl]-4-methylpiperidine

HRID 896539Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][C@@H:13]([CH3:16])[C@H:12]([CH2:17]OS(C)(=O)=O)[CH2:11]2)=[CH:4][CH:3]=1.[N-:23]=[N+:24]=[N-:25].[Na+]>CN(C)C=O>[N:23]([CH2:17][C@H:12]1[C@H:13]([CH3:16])[CH2:14][CH2:15][N:10]([CH2:9][CH2:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:11]1)=[N+:24]=[N-:25]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of methanesulfonic acid trans-{l-[2-(4-fluorophenyl)ethyl]-4-methylpiperidin-3-ylmethyl} ester (the crude material from Part D, about 1.0 mmol) and sodium azide (195 mg, 3 mmol) in N,N-dimethylformamide (4 mL) was stirred at 50° C. for 28 hours. The mixture was cooled to room temperature, filtered, and the solid was rinsed with ethyl acetate. The combined filtrates were diluted with ethyl acetate, and the resulting solution was washed twice with water, dried over sodium sulfate, and concentrated under vacuum. The residue was an orange oil (252 mg, 91%) which was used without further purification. 1H NMR (300 MHz, CDCl3) δ7.17 (m, 2H), 6.98 (t, J=9 Hz, 2H), 3.50 (dd, J=12, 3 Hz, 1H), 3.25 (dd, J=12, 8 Hz, 1H), 3.08 (dm, J=10 Hz, 1H), 3.00 (dm, J=11 Hz, 1H), 2.83 (m, 2H), 2.60 (m, 2H), 2.04 (m, 1H), 1.88 (t, J=11 Hz, 1H), 1.71 (m, 1H), 1.60 (m, 1H), 1.5-1.3 (m, 2H), 1.00 (d, J=7 Hz, 3H).

Workup

temperatureThe mixture was cooled to room temperature
filtrationfiltered
washthe solid was rinsed with ethyl acetate
additionThe combined filtrates were diluted with ethyl acetate
washthe resulting solution was washed twice with water
dry with materialdried over sodium sulfate
concentrationconcentrated under vacuum
customwas used without further purification

Sources & evidence

ORD record: ord-8c117bf0ba724399b3ee9c04540bfd67
Source dataset: uspto-grants-2005_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06919356B2

Reaction notes

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