Piperidine → 1-{[7-(Methylsulfonyl)-4H-1,3-benzodioxin-2-YL]methyl}piperidine

HRID 452412Notes

Reaction equation

Br[CH2:2][CH:3]1[O:8][C:7]2[CH:9]=[C:10]([S:13]([CH3:16])(=[O:15])=[O:14])[CH:11]=[CH:12][C:6]=2[CH2:5][O:4]1.[NH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>CCO>[CH3:16][S:13]([C:10]1[CH:11]=[CH:12][C:6]2[CH2:5][O:4][CH:3]([CH2:2][N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[O:8][C:7]=2[CH:9]=1)(=[O:15])=[O:14]

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 2-(bromomethyl)-7-(methylsulfonyl)-4H-1,3-benzodioxine (0.70 g, 2.28 mmol), piperidine (2.0 ml, 20.2 mmol) and EtOH (4.0 ml) was heated under microwave irradiation at 130° C. for 30 min. The volatiles were evaporated in vacuum and the crude product was chromathographed twice on a silica column using EtOAc as eluent. Collection of the fractions containing pure product and evaporation of the solvent afforded the pure title compound (0.31 g, 49%). The amine was converted into HCl salt and crystallized from MeOH/DEE (0.33 g). M.p. 217° C. 1H-NMR (400 MHz, MeOH): δ 7.49 (1H, dd, J1 8.0 Hz, J22.0 Hz), δ 7.39 (1H, d, J 1.6 Hz), δ 7.31 (1H, d, J 8.0 Hz), δ 5.31 (1H, t, J 5.2 Hz), δ 5.02 (2H, dd, J1 60.4 Hz, J2 15.6 Hz), δ 3.10 (3H, s), δ 2.77 (2H, m), δ 2.60 (4H, s, broad), δ 1.63 (4H, m), δ 1.49 (2H, m).

Workup

customThe volatiles were evaporated in vacuum
customCollection of the fractions
additioncontaining pure
customproduct and evaporation of the solvent

Sources & evidence

ORD record: ord-f363c28fd0294b0fab487840143b8ae3
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08492372B2

Reaction notes

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