Water → 6-Bromo-2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide

HRID 1772668Notes

Reaction equation

HRID 1772668 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:15]=[CH:14][C:7]2[C:8](=[O:13])[NH:9][S:10](=[O:12])(=[O:11])[C:6]=2[CH:5]=1.[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1.O>CN(C=O)C>[Br:3][C:4]1[CH:15]=[CH:14][C:7]2[C:8](=[O:13])[N:9]([CH2:22][C:21]3[CH:24]=[CH:25][C:18]([O:17][CH3:16])=[CH:19][CH:20]=3)[S:10](=[O:12])(=[O:11])[C:6]=2[CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 105409966-Bromo-2,3-dihydro-1,2-benzothiazole-1,1,3-trione

Product 1

HCID 1177280606-Bromo-2-(4-methoxybenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 60% NaH (10.1 mg, 0.254 mmol) in DMF (1 mL), 6-bromobenzo[d]isothiazol-3(2H)-one 1,1-dioxide (55.4 mg, 0.212 mmol) was added portionwise at 0° C. The resulting mixture was stirred at rt for 15 min and p-methoxy benzyl chloride (27.6 μL, 0.212 mmol) was added dropwise. The reaction mixture was heated to 70° C. overnight, allowed to cool to rt, and treated with water (20 mL). The aqueous layer was extracted with EtOAc (3×50 mL) and the combined organic layers were dried over Na2SO4, filtered, and concentrated. The resulting solid was recrystallized from hexane/DCM to obtain compound 38a. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.08 (d, J=1.5 Hz, 1H), 7.89 (dd, J=8.2, 1.6 Hz, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.35 (d, J=8.6 Hz, 2H), 6.79 (d, J=8.6 Hz, 2H), 4.76 (s, 2H), 3.71 (s, 3H).

Workup

  1. additionwas added portionwise at 0° C
  2. temperatureThe reaction mixture was heated to 70° C. overnight
  3. temperatureto cool to rt
  4. extractionThe aqueous layer was extracted with EtOAc (3×50 mL)
  5. dry with materialthe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting solid was recrystallized from hexane/DCM

Sources & evidence

ORD record
ord-aeb91d38e571419ab18f89f257aa22ee
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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