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

HRID 419604Notes

Reaction equation

[CH2:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([O:12][CH2:13][CH3:14])=[CH:5][C:4]=1F)[CH3:2].[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>O>[CH2:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([O:12][CH2:13][CH3:14])=[CH:5][C:4]=1[N:25]1[CH2:26][CH2:27][CH:22]([CH2:21][CH2:20][S:17]([CH3:16])(=[O:19])=[O:18])[CH2:23][CH2:24]1)[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To 1-ethyl-4-(ethyloxy)-2-fluoro-5-nitrobenzene (0.19 g, 0.89 mmol), 4-[2-(methylsulfonyl)ethyl]piperidine (Example 101, Step D) (0.20 g, 1.1 mmol), and K2CO3 (0.43 g, 3.1 mmol) was added DMSO (12 mL). The reaction was heated to 100° C. for two days. Reaction was determined to be complete by TLC. The reaction mixture was diluted with H2O and extracted with DCM and EtOAc sequentially for two iterations. The organic was dried (MgSO4), filtered, and rotovapped down. Purification by flash chromatography provided the title compound of Step B (0.22 g, 0.57 mmol, 65% yield). 1H NMR (400 MHz, CDCl3) δ 7.80 (s, 1H), 6.57 (s, 1H), 4.13 (q, J=6.9 Hz, 2H), 3.20 (d, J=11.6 Hz, 2H), 3.00-3.13 (m, 2H), 2.92 (s, 3H), 2.67 (t, J=11.7 Hz, 2H), 2.57 (q, J=7.4 Hz, 2H), 1.77-1.97 (m, 4H), 1.36-1.68 (m, 6H), 1.24 (t, 3H).

Workup

customReaction
extractionextracted with DCM and EtOAc sequentially for two iterations
dry with materialThe organic was dried (MgSO4)
filtrationfiltered
customPurification by flash chromatography

Sources & evidence

ORD record: ord-1d54f03259074499ba7a912bbd77aa40
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093239B2

Reaction notes

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