1-Acetoxy-2-bromoethane → 2-{4-(1,3-benzodioxol-5-yl)-5-methoxy-3-[(methoxymethyl)(phenethylsulfonyl)amino]-1H-pyrazol-1-yl}ethyl Acetate

HRID 1062809Notes

Reaction equation

HRID 1062809 reaction equation
[H-].[Na+].[O:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3[C:13]([O:32][CH3:33])=[N:14][NH:15][C:16]=3[N:17]([CH2:29][O:30][CH3:31])[S:18]([CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)(=[O:20])=[O:19])=[CH:11][C:6]=2[O:5][CH2:4]1.[C:34]([O:37][CH2:38][CH2:39]Br)(=[O:36])[CH3:35]>O1CCCC1>[C:34]([O:37][CH2:38][CH2:39][N:14]1[C:13]([O:32][CH3:33])=[C:12]([C:10]2[CH:9]=[CH:8][C:7]3[O:3][CH2:4][O:5][C:6]=3[CH:11]=2)[C:16]([N:17]([CH2:29][O:30][CH3:31])[S:18]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)(=[O:20])=[O:19])=[N:15]1)(=[O:36])[CH3:35]

Participants

5

Reactant 3

HCID 135641-Acetoxy-2-bromoethane2×HCID 24758Sodium hydride2×HCID 22282022N-[4-(1,3-benzodioxol-5-yl)-3-methoxy-1H-pyrazol-5-yl]-N-(methoxymethyl)-2-phenyl-1-ethanesulfonamide

Product 1

HCID 222819772-{4-(1,3-benzodioxol-5-yl)-5-methoxy-3-[(methoxymethyl)(phenethylsulfonyl)amino]-1H-pyrazol-1-yl}ethyl Acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% dispersion in oil, 162 mg) was added at room temperature under an atmosphere of nitrogen to a solution of N-[4-(1,3-benzodioxol-5-yl)-3-methoxy-1H-pyrazol-5-yl]-N-(methoxymethyl)-2-phenyl-1-ethanesulfonamide (Preparation 55) in anhydrous tetrahydrofurane. After 10 minutes, 2-bromoethyl acetate (446 μl) was added and the reaction mixture was refluxed overnight. At room temperature, some more 2-bromoethylacetate (446 μl) was added and the reaction was refluxed for 24 h. Then at room temperature, some more sodium hydride (50 mg) was added and the reaction was refluxed for 24 h. At room temperature, the reaction was quenched by the addition of an aqueous saturated solution of ammonium chloride (5 ml), water (10 ml) and the mixture was extracted with ethyl acetate (3×10 ml). The combined organic fractions were washed with brine (20 ml), dried on sodium sulfate and concentrated under reduced pressure to yield a dark oil which was purified by column chromatography (silica, 10 g), eluted with hexane:ethyl acetate (4:1) then (2:1) yielding the title compound as a colourless oil (92 mg).

Workup

  1. temperaturethe reaction mixture was refluxed overnight
  2. temperaturethe reaction was refluxed for 24 h
  3. temperaturethe reaction was refluxed for 24 h
  4. customAt room temperature, the reaction was quenched by the addition of an aqueous saturated solution of ammonium chloride (5 ml), water (10 ml)
  5. extractionthe mixture was extracted with ethyl acetate (3×10 ml)
  6. washThe combined organic fractions were washed with brine (20 ml)
  7. customdried on sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customto yield a dark oil which
  10. customwas purified by column chromatography (silica, 10 g)
  11. washeluted with hexane:ethyl acetate (4:1)

Sources & evidence

ORD record
ord-1b3d36e57e5449d485ade2d83092823e
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

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