Cesium carbonate → N-(4-methoxybenzyl)-2-(methoxymethyl)-3-oxo-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528646Notes

Reaction equation

HRID 528646 reaction equation
Cl[CH:2]([CH2:6][O:7][CH3:8])[C:3](Cl)=[O:4].[NH2:9][C:10]1[CH:15]=[CH:14][C:13]([S:16]([N:19]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:20]2[S:21][CH:22]=[CH:23][N:24]=2)(=[O:18])=[O:17])=[CH:12][C:11]=1[OH:34].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[CH3:33][O:32][C:29]1[CH:28]=[CH:27][C:26]([CH2:25][N:19]([C:20]2[S:21][CH:22]=[CH:23][N:24]=2)[S:16]([C:13]2[CH:14]=[CH:15][C:10]3[NH:9][C:3](=[O:4])[CH:2]([CH2:6][O:7][CH3:8])[O:34][C:11]=3[CH:12]=2)(=[O:18])=[O:17])=[CH:31][CH:30]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 874933872-Chloro-3-methoxypropanoyl chlorideHCID 89761412HCID 89761412, compound

Product 1

HCID 89761918N-(4-methoxybenzyl)-2-(methoxymethyl)-3-oxo-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideYield 39.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-chloro-3-methoxypropanoyl chloride (500 mg, 3.18 mmol) and 4-amino-3-hydroxy-N-(4-methoxybenzyl)-N-(thiazol-2-yl)benzenesulfonamide (Intermediate AD; 1.04 g, 2.65 mmol) in DMF (20 mL) was added Cs2CO3 (2.59 g, 7.95 mmol). The reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude material which was further purified by column chromatography (silica gel 100-200 mesh and 0-30% ethyl acetate in hexane) to obtain N-(4-methoxybenzyl)-2-(methoxymethyl)-3-oxo-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (500 mg, 33.1%) as an off white solid. m/z (ESI) 476.1 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (2×100 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto obtain the crude material which
  6. customwas further purified by column chromatography (silica gel 100-200 mesh and 0-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-f1aa88aba60b48749d4e3ab44692943f
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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