Water → 1-[2-(Methanesulfonyl)ethyl]-4-(5-methoxy-2-methyl-4-nitrophenyl)piperazine

HRID 419502Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[C:7](F)[C:6]([CH3:10])=[CH:5][C:4]=1[N+:11]([O-:13])=[O:12].C([O-])([O-])=O.[K+].[K+].Cl.[CH3:21][S:22]([CH2:25][CH2:26][N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)(=[O:24])=[O:23].O>CS(C)=O>[CH3:10][C:6]1[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[C:3]([O:2][CH3:1])=[CH:8][C:7]=1[N:30]1[CH2:29][CH2:28][N:27]([CH2:26][CH2:25][S:22]([CH3:21])(=[O:23])=[O:24])[CH2:32][CH2:31]1

Participants

Conditions

Temperature: 100 °C

Procedure

5-fluoro-4-methyl-2-nitrophenyl methyl ether (Example 113, step B) (5.0 g, 27 mmol), K2CO3 (11.2 g, 81 mmol), and 1-[2-(methylsulfonyl)ethyl]piperazine hydrochloride (8.0 g, 35 mmol) were weighed into a 150 mL sealed tube, taken up in 85 mL of DMSO and heated to 100° C. for 24 h. The mixture was poured into 500 mL of H2O, filtered, washed with H2O, air dried for 15 min, washed with hexanes (200 mL), washed with 20% Ether/Hexanes (200 mL), and air dried for 2 h to give the title compound of step C (6.6 g, 18.5 mmol, 68%). An additional (540 mg, 5.5%) of product was obtained by extraction of the H2O layer, followed by flash chromatography. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.75 (s, 1H), 6.70 (s, 1H), 3.90 (s, 3H), 3.31-3.35 (m, 2H), 3.04 (s, 3H), 2.99-3.03 (m, 4H), 2.77 (t, J=6.60 Hz, 2H), 2.56-2.63 (m, 4H), 2.19 (s, 3H).

Workup

customsealed tube
filtrationfiltered
washwashed with H2O, air
customdried for 15 min
washwashed with hexanes (200 mL)
washwashed with 20% Ether/Hexanes (200 mL), and air
customdried for 2 h

Sources & evidence

ORD record: ord-88e96f197c7b40c29db7cc6804a768fb
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093239B2

Reaction notes

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