Cesium carbonate → 3-Bromo-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoic acid methyl ester

HRID 1454199Notes

Reaction equation

HRID 1454199 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9](I)[CH:10]=1)[C:5]([O-:7])=[O:6].[C:12](=O)([O-])[O-].[Cs+].[Cs+].[S:18]1(=[O:25])(=[O:24])[CH2:23][CH2:22][CH2:21][CH2:20][NH:19]1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:12][O:7][C:5](=[O:6])[C:4]1[CH:8]=[C:9]([N:19]2[CH2:20][CH2:21][CH2:22][CH2:23][S:18]2(=[O:25])=[O:24])[CH:10]=[C:2]([Br:1])[CH:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 3035081,4-ButanesultamHCID 69315153-Bromo-5-iodobenzoate

Product 1

HCID 575293223-Bromo-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoic acid methyl esterYield 84%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

To a sealable tube equipped with a stir bar were added 3-bromo-5-iodobenzoate (2.0 g, 5.88 mmol), cesium carbonate (2.85 g, 8.82 mmol), tris(dibenzylideneacetone)dipalladium (0) (27.1 mg, 0.029 mmol) and xant phos (51 mg, 0.088 mmol) in toluene (45 mL) followed by [1,2]thiazinane 1,1-dioxide (902 mg, 6.47 mmol). The resulting mixture was stirred at 10° C. for 16 h, cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution, dried over magnesium sulfate, filtered and concentrated under vacuum. The crude mixture was purified by reverse phase prep HPLC to give the title compound (1.7 g, 84% yield): 1H NMR (CD3OD, 500 MHz) δ ppm 1.93-1.97 (2H, m), 2.30-2.35 (2H, m), 3.30 (2H, t, J=5 Hz), 3.78 (2H, t, J=5 Hz), 3.94 (3H, s), 7.76 (1H, m), 7.93 (1H, m), 8.06 (1H, m). HPLC retention time: 1.772 min (method A). MS (ESI) (M+H)+ 348.06.

Workup

  1. customTo a sealable tube equipped with a stir bar
  2. temperaturecooled to room temperature
  3. washThe organic phase was washed with saturated sodium bicarbonate solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude mixture was purified by reverse phase prep HPLC

Sources & evidence

ORD record
ord-627f56b94c5045848639a13c7319b55c
Source dataset
uspto-grants-2009_01
Patent number
US07476764B2

Reaction notes

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