Hydroxylamine → Cgs-27023

HRID 742062

Reaction equation

HRID 742062 reaction equation
C(Cl)(=O)C(Cl)=O.Cl.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([S:16]([N:19]([CH2:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[C@H:20]([CH:24]([CH3:26])[CH3:25])[C:21](O)=[O:22])(=[O:18])=[O:17])=[CH:12][CH:11]=1.[NH2:34][OH:35]>C(Cl)Cl.CN(C)C=O.O1CCCC1>[OH:35][NH:34][C:21](=[O:22])[C@H:20]([N:19]([S:16]([C:13]1[CH:14]=[CH:15][C:10]([O:9][CH3:8])=[CH:11][CH:12]=1)(=[O:18])=[O:17])[CH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1)[CH:24]([CH3:26])[CH3:25]

Participants

7

Reactant 3

HCID 787HydroxylamineHCID 65578Oxalyl chlorideHCID 700617032(R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3-methyl-butanoic acid hydrochloride

Product 1

HCID 446504Cgs-27023

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Oxalyl chloride (106 mL, 1.22 mol) is added over 1 hour to dimethylformamide (92 mL) in methylene chloride (1250 mL) at 0° C. To this is added a solution of 2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3-methylbutanoic acid hydrochloride (248 g, 0.6 mol) in dimethylformamide (450 mL) over 1 hour, maintaining the temperature at 0° C. This solution is stirred an additional 2 hours at room temperature, and then added dropwise to a mixture of hydroxylamine (460 g of a 50% aqueous solution, 6.82 mol) in tetrahydrofuran (2400 mL). The reaction is stirred an additional 3 hours at 5° C., and then at room temperature overnight. The reaction mixture is filtered, the organic layer is collected, and the solvent is evaporated. The crude product is re-dissolved in methylene chloride (2 L), washed with water (2×1 L), saturated sodium bicarbonate (4×1 L), brine (1 L), dried (Na2SO4), and the solvent is evaporated. The product is dissolved in ethyl acetate (700 mL) and diluted with ether (1400 mL) to induce precipitation. The pure product is collected by filtration to provide N-hydroxy-2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3-methylbutanamide. After conversion to the hydrochloride salt, a white solid is obtained, m.p. 169°-170° C. (dec).

Workup

  1. stirringThe reaction is stirred an additional 3 hours at 5° C.
  2. customat room temperature
  3. customovernight
  4. filtrationThe reaction mixture is filtered
  5. customthe organic layer is collected
  6. customthe solvent is evaporated
  7. dissolutionThe crude product is re-dissolved in methylene chloride (2 L)
  8. washwashed with water (2×1 L), saturated sodium bicarbonate (4×1 L), brine (1 L)
  9. dry with materialdried (Na2SO4)
  10. customthe solvent is evaporated
  11. dissolutionThe product is dissolved in ethyl acetate (700 mL)
  12. additiondiluted with ether (1400 mL)
  13. customprecipitation
  14. filtrationThe pure product is collected by filtration

Sources & evidence

ORD record
ord-17f026765bef471c94e607a2a4d1a56c
Source dataset
uspto-grants-1996_09
Patent number
US05552419

Linked notes

Loading…