Methyl vinyl sulfone → (2S)-2-(1-methylethyl)-4-[3-(methyloxy)-4-nitrophenyl]-1-[2-(methylsulfonyl)-ethyl]piperazine

HRID 419674Notes

Reaction equation

[CH3:1][CH:2]([C@@H:4]1[NH:9][CH2:8][CH2:7][N:6]([C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[C:12]([O:19][CH3:20])[CH:11]=2)[CH2:5]1)[CH3:3].[CH:21]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH2:22]>O1CCOCC1>[CH3:3][CH:2]([C@H:4]1[CH2:5][N:6]([C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[C:12]([O:19][CH3:20])[CH:11]=2)[CH2:7][CH2:8][N:9]1[CH2:22][CH2:21][S:23]([CH3:26])(=[O:25])=[O:24])[CH3:1]

Participants

Conditions

Temperature: 60 °C

Procedure

(3S)-3-(1-Methylethyl)-1-[3-(methyloxy)-4-nitrophenyl]piperazine (0.355 g, 1.27 mmol) was dissolved in 15 mL of dioxane with stirring. Methyl vinyl sulfone (0.34 mL, 3.88 mmol) was added via syringe. The reaction was heated to 60° C. for 2.5 days. Additional methyl vinyl sulfone (0.68 mL, 7.76 mmol) was added, and the heat was increased to 90° C. The reaction was maintained at that temperature for one week. The reaction was cooled to rt and concentrated onto silica gel. Purification by flash chromatography afforded the title compound of step G (0.383 g, 0.994 mmol, 78%). 1H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J=9.5 Hz, 1H), 6.53 (dd, J=9.5, 2.4 Hz, 1H), 6.40 (d, J=2.4 Hz, 1H), 3.86 (s, 3H), 3.77 (d, J=12.5 Hz, 1H), 3.66 (br. s., J=12.5 Hz, 1H), 3.28-3.39 (m, 1H), 3.13-3.24 (m, 1H), 3.00-3.13 (m, 2H), 2.88-3.00 (m, 5H), 2.77-2.88 (m, 1H), 2.39-2.51 (m, 1H), 2.17-2.26 (m, 1H), 1.93-2.07 (m, 1H), 0.96 (d, J=6.8 Hz, 3H), 0.85 (d, J=6.8 Hz, 3H).

Workup

temperaturethe heat was increased to 90° C
temperatureThe reaction was maintained at that temperature for one week
temperatureThe reaction was cooled to rt
concentrationconcentrated onto silica gel
customPurification by flash chromatography

Sources & evidence

ORD record: ord-2c674ff8657a4b6eac2cb904b31f2fa2
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093239B2

Reaction notes

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