Dimethyl Sulfoxide → 1-[5-(Ethyloxy)-2-methyl-4-nitrophenyl]-4-[2-(methylsulfonyl)ethyl]piperidine

HRID 419627Notes

Reaction equation

[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([O:11][CH2:12][CH3:13])=[CH:4][C:3]=1F.Cl.[CH3:16][S:17]([CH2:20][CH2:21][CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)(=[O:19])=[O:18].C([O-])([O-])=O.[K+].[K+].CS(C)=O>CCOC(C)=O.C(Cl)Cl>[CH2:12]([O:11][C:5]1[C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]([CH3:1])=[C:3]([N:25]2[CH2:26][CH2:27][CH:22]([CH2:21][CH2:20][S:17]([CH3:16])(=[O:19])=[O:18])[CH2:23][CH2:24]2)[CH:4]=1)[CH3:13]

Participants

Conditions

Temperature: 100 °C

Procedure

To 1-(ethyloxy)-5-fluoro-4-methyl-2-nitrobenzene (Example 215, step A) (13.1 g, 65.9 mmol), 4-[2-(methylsulfonyl)ethyl]piperidine hydrochloride (15.0 g, 65.9 mmol) and K2CO3 (31.9 g, 231 mmol) was added DMSO (300 mL). The reaction mixture was heated at 100° C. overnight. The reaction was cooled to rt and diluted with EtOAc and DCM. The organic layer was washed with H2O and the aqueous layer was backextracted with DCM. The combined organic layers were dried (MgSO4), filtered and rotovapped down. Purification by flash chromatography provided the title compound of Step F (16.2 g, 43.6 mmol, 66% yield). This reaction was carried out in duplicate to provide an overall amount of 33.2 g, 89.4 mmol of the title compound of Step F. 1H NMR (400 MHz, DMSO-d6) δ 7.79 (s, 1H), 6.56-6.73 (m, 1H), 4.16 (q, J=7.0 Hz, 2H), 3.30 (d, J=12.2 Hz, 2H), 3.04-3.15 (m, 2H), 2.95 (s, 3H), 2.74 (t, J=11.5 Hz, 2H), 2.26 (s, 3H), 1.81-1.97 (m, 4H), 1.42-1.74 (m, 6H).

Workup

temperatureThe reaction was cooled to rt
washThe organic layer was washed with H2O
dry with materialThe combined organic layers were dried (MgSO4)
filtrationfiltered
customPurification by flash chromatography

Sources & evidence

ORD record: ord-406f3a43664b4e0c9ec7227c32d19847
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093239B2

Reaction notes

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