Cesium carbonate → 5-Bromo-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

HRID 515212Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:9][S:8](=[O:11])(=[O:10])[N:7]([CH3:12])[C:6]=2[CH:13]=1.CN1[C:19](=O)[CH2:18][CH2:17][CH2:16]1.C(=O)([O-])[O-].[Cs+].[Cs+].BrCC1CC1>C(OCC)(=O)C.O1CCOCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]([CH2:16][CH:17]3[CH2:19][CH2:18]3)[S:8](=[O:11])(=[O:10])[N:7]([CH3:12])[C:6]=2[CH:13]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a round bottom flask was added 6-bromo-1-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (1-3) (5.32 g, 20.2 mmol), anhydrous NMP (10 mL), anhydrous 1,4 Dioxane (100 mL), cesium carbonate (13.2 g, 40.4 mmol), followed by (bromomethyl)cyclopropane (3.00 g, 22.2 mmol). The reaction mixture was then heated to 100° C. while stirring in a hot oil bath for 18 hours. The crude reaction mixture was then cooled to room temperature, then suspended in ethyl acetate and washed with a saturated solution of sodium bicarbonate, followed by water, then brine, dried over sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel chromatography (0-40% EtOAc/Hex) to give 5-bromo-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (1-4) as a tan solid. HRMS (M+H)+: observed=316.9953, calculated=316.9954.

Workup

customThe crude reaction mixture
temperaturewas then cooled to room temperature
washwashed with a saturated solution of sodium bicarbonate
dry with materialbrine, dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe resulting residue was purified by silica gel chromatography (0-40% EtOAc/Hex)

Sources & evidence

ORD record: ord-fa054024c3644edc99f2ed9975e7506f
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108937B2

Reaction notes

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