Sodium hydride → Methyl N-[4-(5-fluorobenzothiazol-2-ylmethoxy)-2-methylphenyl]carbamate

HRID 1597823Notes

Reaction equation

HRID 1597823 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:14])[O:12][CH3:13])=[C:6]([CH3:15])[CH:5]=1.Br[CH2:17][C:18]1[S:19][C:20]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:21]=2[N:22]=1.[Cl-].[NH4+]>CN(C)C=O>[F:27][C:24]1[CH:25]=[CH:26][C:20]2[S:19][C:18]([CH2:17][O:3][C:4]3[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:14])[O:12][CH3:13])=[C:6]([CH3:15])[CH:5]=3)=[N:22][C:21]=2[CH:23]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 144586272-(Bromomethyl)-5-fluorobenzo[d]thiazoleHCID 18932138methyl N-(4-hydroxy-2-methylphenyl)carbamate

Product 1

HCID 18932120Methyl N-[4-(5-fluorobenzothiazol-2-ylmethoxy)-2-methylphenyl]carbamateYield 67.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

54.6 mg of sodium hydride (as a 60% w/w dispersion in mineral oil) were added to a solution of 204.9 mg of methyl N-(4-hydroxy-2-methylphenyl)carbamate [prepared as described in Example 15(a) above] in 5 ml of dimethylformamide cooled in an ice-water bath. The resulting mixture was stirred at the same temperature for 5 minutes, and then 366.2 mg of 2-bromomethyl-5-fluorobenzothiazole [prepared as described in step (a) above] were added. The temperature of the resulting mixture was elevated to room temperature and the mixture was stirred for 1.5 hours. At the end of this time, a saturated aqueous ammonium chloride solution was added to the reaction mixture and the resulting mixture was extracted with ethyl acetate. The resulting extract was washed consecutively with water and a saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The solvent was then removed by evaporation under reduced pressure to give a crude crystalline solid which was purified by column chromatography through silica gel using a 3:1 by volume mixture of hexane and ethyl acetate as the eluent to give 263.3 mg (yield 65%) of the title compound as a solid having a melting point of 165° to 168° C.

Workup

  1. temperaturecooled in an ice-water bath
  2. customwas elevated to room temperature
  3. stirringthe mixture was stirred for 1.5 hours
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. extractionThe resulting extract
  6. washwas washed consecutively with water
  7. dry with materiala saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate
  8. customThe solvent was then removed by evaporation under reduced pressure
  9. customto give a crude crystalline solid which
  10. customwas purified by column chromatography through silica gel using a 3:1
  11. additionby volume mixture of hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-f747f82a6744446dac7e8bffd6fef2b9
Source dataset
uspto-grants-1998_04
Patent number
US05736487

Reaction notes

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