1,2-Dibromoethane → 2,3-Dihydro-1,4-benzothiazine

HRID 1455296Notes

Reaction equation

HRID 1455296 reaction equation
C([O-])([O-])=O.[K+].[K+].Br[CH2:8][CH2:9]Br.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[SH:18]>CC(C)=O>[S:18]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[NH:11][CH2:9][CH2:8]1

Participants

5

Reactant 3

HCID 78391,2-DibromoethaneHCID 87132-AminothiophenolHCID 11430Potassium Carbonate

Product 1

HCID 1510642,3-Dihydro-1,4-benzothiazineYield 66.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

K2CO3 (4.4 g, 31.9 mmol) and 1,2-dibromoethane (0.69 mL, 8.0 mmol) were added to a solution of 2-aminothiophenol (1.0 g, 8.0 mmol) in 20 mL of acetone at room temperature. The reaction mixture was stirred overnight. The insoluble material was filtered off and the solvent was removed under reduced pressure. The residue was purified on silica gel column to provide 3,4-dihydro-2H-1,4-benzothiazine (0.8 g, 66%). MS (ES+): 152 (M+1). (208b) K2CO3 (5.2 g, 37.7 mmol) and methyl 4-(bromomethyl)benzoate (2.8 g, 12.6 mmol) were added to a solution of 208a (1.9 g, 12.6 mmol) in 20 mL of anhydrous DMF. The reaction mixture was heated to 80° C. overnight. After cooling down, the solid was filtered off and rinsed with DMF. The solvent was removed under reduced pressure and the residue was purified on silica gel column to provide methyl 4-(2,3-dihydro-4H-1,4-benzothiazin-4-ylmethyl)benzoate (3.02 g, 80%). MS (ES+): 300 (M+1). (208c) A solution of Oxone® (2.2 g, 3.54 mmol) in 20 mL of H2O was added slowly to a solution of 208b (2.12 g, 7.1 mmol) in 20 mL of MeOH. Upon completion of the reaction, the solution was diluted with ethyl acetate, washed with saturated NaHCO3 and dried over MgSO4. After filtration and concentration, the residue was purified on silica gel column to provide methyl 4-[(1-oxido-2,3-dihydro-4H-1,4-benzothiazin-4-yl)methyl]benzoate (1.39 g, 65%). MS (AP+): 316 (M+1). (208d) A solution of KOH (1N, 7.5 mL) was added to a solution of 208c (1.25 g, 3.8 mmol) in 40 mL of MeOH and 40 mL of H2O. The reaction mixture was heated to 60° C. overnight. Upon completion, the aliquot was neutralized with HCl (1N, 1.2 mL). The solvent was removed and the residue was dissolved in MeOH. After filtration and concentration, 4-(2,3-dihydro-4H-1,4-benzothiazin-4-ylmethyl)benzoic acid was obtained in quantitative yield. MS (AP+): 318 (M+1).

Workup

  1. filtrationThe insoluble material was filtered off
  2. customthe solvent was removed under reduced pressure
  3. customThe residue was purified on silica gel column

Sources & evidence

ORD record
ord-b07ba13fee484305911e2402926c1ff1
Source dataset
uspto-grants-2009_01
Patent number
US07482372B2

Reaction notes

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