Hydroxylamine → HCID 22644749, compound

HRID 2414617Notes

Reaction equation

HRID 2414617 reaction equation
[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([NH:15][CH:16]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:22][CH:21]=2)[C:17](O)=[O:18])(=[O:14])=[O:13])=[CH:8][CH:7]=1)[C:2]#[C:3][CH3:4].CN(C=O)C.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[NH2:52][OH:53]>ClCCl.C1COCC1>[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([NH:15][CH:16]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33]3)=[CH:22][CH:21]=2)[C:17]([NH:52][OH:53])=[O:18])(=[O:13])=[O:14])=[CH:8][CH:7]=1)[C:2]#[C:3][CH3:4]

Participants

8

Reactant 5

HCID 787HydroxylamineHCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 22644962HCID 22644962, compound

Product 1

HCID 22644749HCID 22644749, compoundYield 20.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° solution of ({[4-(2-butynyloxy)phenyl]sulfonyl}amino){4-[2-(1-pyrrolidinyl)ethoxy]phenyl}acetic acid (1.58 g, 3.35 mmol) and DMF (0.52 ml, 6.69 mmol) in dichloromethane (29 ml) was added oxalyl chloride (3.35 ml of 2M in CH2Cl2; 6.69 mmol). The reaction mixture was stirred at 0° C. for 10 minutes and at room temperature for 2 h, then cooled again. A THF (2 ml) solution of triethylamine (1.87 ml 13.38 mmol) and hydroxylamine (2.05 mL of 50% hydroxylamine in water, 33.5 mmol) was added in one portion. The reaction was stirred at room temperature overnight. After removing the solvent, the oily residue was extracted with ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and evaporated. Preparative TLC chromatography eluting with dichloromethane:methanol (8:2) provided 0.33 g of 2-({[4-(2-butynyloxy)phenyl]-sulfonyl}amino)-N-hydroxy-2-{4-[2-(1-pyrrolidinyl)ethoxy]phenyl}acetamide. mp 70° C. This compound (0.28 g, 0.57 mmol) was dissolved in dichloromethane (3 ml) and methanol (2 ml) cooled in ice bath. Then 1M hydrogen chloride in ethyl ether (0.86 ml, 0.86 mmol) was dropped in. The mixture was stirred at 0°C. for 10 minutes and at room temperature for 15 h, and then concentrated to obtain 0.27 g of the hydrochloride salt. mp 68-70° C. Electrospray Mass Spec 488.1 (M+H)+.

Workup

  1. temperaturecooled again
  2. stirringThe reaction was stirred at room temperature overnight
  3. customAfter removing the solvent
  4. extractionthe oily residue was extracted with ethyl acetate and water
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. washPreparative TLC chromatography eluting with dichloromethane:methanol (8:2)

Sources & evidence

ORD record
ord-3354b6db68884766bdd6a86a36cda38e
Source dataset
uspto-grants-2004_11
Patent number
US06812227B2

Reaction notes

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