N-bromobutanimide → 4-(4-Amino-3-bromo-phenyl)-1,1-dioxo-hexahydro-1lambda6-thiopyran-4-carbonitrile

HRID 1054290Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:16]#[N:17])[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C1C(=O)N([Br:25])C(=O)C1>C(Cl)Cl>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:16]#[N:17])[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[Br:25]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 4-(4-amino-phenyl)-1,1-dioxo-hexahydro-1λ6-thiopyran-4-carbonitrile (114 mg, 0.455 mmol, as prepared in the previous step) in CH2Cl2 (15 mL) was cooled to 0° C., treated with solid NBS (77.0 mg, 0.433 mmol), and stirred at that temperature for 30 min. The mixture was diluted with CH2Cl2 (20 mL) and washed with satd aq NaHCO3 (1×20 mL). The aqueous layer was extracted with CH2Cl2 (1×20 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 50% EtOAc-hexane afforded the title compound (136 mg, 90%) as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 7.53 (d, 1H, J=2.0 Hz), 7.23 (dd, 1H, J=8.4, 2.0 Hz), 6.79 (d, 1H, J=8.0 Hz), 4.40-4.15 (br s, 2H), 3.60-3.45 (m, 2H), 3.26-3.11 (m, 2H), 2.78-2.63 (m, 2H), 2.51-2.38 (m, 2H).

Workup

washwashed with satd aq NaHCO3 (1×20 mL)
extractionThe aqueous layer was extracted with CH2Cl2 (1×20 mL)
dry with materialThe combined organic layers were dried over MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-e46b467b819f452b87005f6de0b6ec69
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394289B2

Reaction notes

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