Water → HCID 86731273, compound

HRID 2277209Notes

Reaction equation

HRID 2277209 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:25]=[CH:24][C:9]([C:10]([NH:12][CH:13]3[CH:22](O)[CH2:21][CH2:20][C:15]4([O:19][CH2:18][CH2:17][O:16]4)[CH2:14]3)=[O:11])=[CH:8][C:7]=2[F:26])[CH2:3][CH2:2]1.C(N(CC)CC)C.O>CS(C)=O>[CH:1]1([CH2:4][O:5][C:6]2[CH:25]=[CH:24][C:9]([C:10]3[O:11][C:22]4[CH2:21][CH2:20][C:15]5([O:16][CH2:17][CH2:18][O:19]5)[CH2:14][C:13]=4[N:12]=3)=[CH:8][C:7]=2[F:26])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 962WaterHCID 8471TriethylamineHCID 86731272HCID 86731272, compound

Product 1

HCID 86731273HCID 86731273, compoundYield 44.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 4-(cyclopropylmethoxy)-3-fluoro-N-(8-hydroxy-1,4-dioxaspiro[4.5]dec-7-yl)benzamide (14.2 g) in dimethyl sulfoxide (100 mL) were added triethylamine (16.3 mL) and sulfur trioxide-pyridine complex (18.6 g), and the mixture was stirred for 1 hr under a nitrogen stream. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To a solution of the obtained residue in THF (100 mL) was added (methoxycarbonylsulfamoyl)triethylammonium hydroxide inner salt (14.0 g), and the mixture was stirred at 60° C. for 1 hr. To the reaction mixture was added saturated brine, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and subjected to silica gel column chromatography (NH, ethyl acetate). The solvent was evaporated, and the obtained solid was washed with diethyl ether to give the title compound (6.00 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. additionTo a solution of the obtained residue in THF (100 mL) was added (methoxycarbonylsulfamoyl)triethylammonium hydroxide inner salt (14.0 g)
  6. stirringthe mixture was stirred at 60° C. for 1 hr
  7. additionTo the reaction mixture was added saturated brine
  8. extractionthe mixture was extracted with ethyl acetate
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated
  11. washthe obtained solid was washed with diethyl ether

Sources & evidence

ORD record
ord-360e90075fb849b5a78f0e6202a40056
Source dataset
uspto-grants-2015_09
Patent number
US09133129B2

Reaction notes

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