Diisopropylethylamine → 4-[4-(4-fluorophenoxy)benzenesulfonylamino]tetrahydropyran-4-carboxylic acid N-benzyloxyamide

HRID 2288109Notes

Reaction equation

HRID 2288109 reaction equation
C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[F:37][C:38]1[CH:63]=[CH:62][C:41]([O:42][C:43]2[CH:48]=[CH:47][C:46]([S:49]([NH:52][C:53]3([C:59]([OH:61])=O)[CH2:58][CH2:57][O:56][CH2:55][CH2:54]3)(=[O:51])=[O:50])=[CH:45][CH:44]=2)=[CH:40][CH:39]=1.Cl.[CH2:65]([O:72][NH2:73])[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1>CN(C)C=O>[CH2:65]([O:72][NH:73][C:59]([C:53]1([NH:52][S:49]([C:46]2[CH:45]=[CH:44][C:43]([O:42][C:41]3[CH:62]=[CH:63][C:38]([F:37])=[CH:39][CH:40]=3)=[CH:48][CH:47]=2)(=[O:50])=[O:51])[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1)=[O:61])[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 102312Benzyloxyamine hydrochlorideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 21868557Y86EH62Njl

Product 1

HCID 538920814-[4-(4-fluorophenoxy)benzenesulfonylamino]tetrahydropyran-4-carboxylic acid N-benzyloxyamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diisopropyl ethylamine (3.89 grams, 0.030 mole) and (benzotriazol-1-yloxy)tris-(dimethylamino)-phosphonium hexafluorophosphate (13.27 grams, 0.030 mole) were added sequentially to a solution of 4-[4-(4-fluorophenoxy)-benzenesulfonylamino] tetrahydropyran-4-carboxylic acid (11.22 grams, 0.028 mole) in anhydrous N,N-dimethylformamide (140 mL). The resulting solution was stirred at room temperature for 16 hours. Additional diisopropyl ethylamine (4.0 mL, 0.051 mole) and O-benzyl hydroxylamine hydrochloride (5.46 grams, 0.034 mole) were then added and the resulting mixture was stirred at 60° C. for 18 hours. After concentration under vacuum, the residue was treated with 0.5N aqueous hydrochloric acid solution and extracted with ethyl acetate. The organic extract was washed with saturated aqueous sodium bicarbonate solution, water, and brine. The solution was dried over magnesium sulfate, filtered and concentrated to one fourth original volume. Addition of an equal volume of hexane precipitated 4-[4-(4-fluorophenoxy)benzenesulfonylamino]-tetrahydropyran-4-carboxylic acid N-benzyloxyamide (11.595 g, 81.6%) as a white crystalline solid (mp 175-176° C.).

Workup

  1. stirringthe resulting mixture was stirred at 60° C. for 18 hours
  2. concentrationAfter concentration under vacuum
  3. additionthe residue was treated with 0.5N aqueous hydrochloric acid solution
  4. extractionextracted with ethyl acetate
  5. extractionThe organic extract
  6. washwas washed with saturated aqueous sodium bicarbonate solution, water, and brine
  7. dry with materialThe solution was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to one fourth original volume
  10. additionAddition of an equal volume of hexane
  11. customprecipitated 4-[4-(4-fluorophenoxy)benzenesulfonylamino]-tetrahydropyran-4-carboxylic acid N-benzyloxyamide (11.595 g, 81.6%) as a white crystalline solid (mp 175-176° C.)

Sources & evidence

ORD record
ord-74034e25d23740789a7911d43686178a
Source dataset
uspto-grants-2000_07
Patent number
US06087392

Reaction notes

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