1-Bromo-2-Chloroethane → 1-(2-chloroethyl)-5-fluoro-3-(1-methylethyl)-3,4-dihydro-1H-2,1,3-benzothiadiazine-2,2-dioxide
Reaction equation
[F:1][C:2]1[C:7]2[CH2:8][N:9]([CH:14]([CH3:16])[CH3:15])[S:10](=[O:13])(=[O:12])[NH:11][C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:20][CH2:21][Cl:22]>CN(C=O)C>[Cl:22][CH2:21][CH2:20][N:11]1[C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([F:1])[C:7]=2[CH2:8][N:9]([CH:14]([CH3:16])[CH3:15])[S:10]1(=[O:13])=[O:12]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of 5-fluoro-3-(1-methylethyl)-3,4-dihydro-1H-2,1,3-benzothiadiazine-2,2-dioxide (0.22 g, 0.9 mmol) in dry DMF (15 ml) was added via cannula to a flask containing NaH (25 mg, 0.99 mmol) and DMF (7 ml) in argon atmosphere, and stirred for 2 hours at room temperature. 1-Bromo-2-chloroethane (0.19 ml, 2.25 mmol,) was then added dropwise and the mixture stirred at room temperature for 4 days. Then, the mixture was extracted with EtOAc (3×50 ml). The combined organic extracts were washed with water (1×100 ml) and then brine (1×100 ml), dried over Na2SO4 and solvent evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (EtOAc:Hexane 1:4) affording pure 1-(2-chloroethyl)-5-fluoro-3-(1-methylethyl)-3,4-dihydro-1H-2,1,3-benzothiadiazine-2,2-dioxide.
Workup
- stirringthe mixture stirred at room temperature for 4 days
- extractionThen, the mixture was extracted with EtOAc (3×50 ml)
- washThe combined organic extracts were washed with water (1×100 ml)
- dry with materialbrine (1×100 ml), dried over Na2SO4 and solvent
- customevaporated under reduced pressure
- customThe residue was purified by flash chromatography on silica gel (EtOAc:Hexane 1:4)
Sources & evidence
- ORD record
- ord-795590fb476d45d8bd450bdef0f2aaff
- Source dataset
- uspto-grants-1999_07
- Patent number
- US05929072
Reaction notes
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