Hydroxylamine → N-hydroxy-4-({4-[(5-hydroxy-2-pentynyl)oxy]phenyl}sulfonyl)-2,2-dimethyl-3-thiomorpholine carboxamide

HRID 2414652Notes

Reaction equation

HRID 2414652 reaction equation
[CH3:1][C:2]1([CH3:33])[S:7][CH2:6][CH2:5][N:4]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]#[C:20][CH2:21][CH2:22][O:23]C3CCCCO3)=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH:3]1[C:30](O)=[O:31].[OH:34][N:35]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.NO>ClCCl.CN(C=O)C.C(OCC)(=O)C.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>[OH:34][NH:35][C:30]([CH:3]1[C:2]([CH3:33])([CH3:1])[S:7][CH2:6][CH2:5][N:4]1[S:8]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]#[C:20][CH2:21][CH2:22][OH:23])=[CH:13][CH:12]=1)(=[O:10])=[O:9])=[O:31]

Participants

9

Reactant 4

HCID 787HydroxylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 226449072,2-dimethyl-4-[(4-{[5-(tetrahydro-2H-pyran-2-yloxy)2-pentynyl]oxy}phenyl)sulfonyl]-3-thiomorpholine carboxylic acid

Product 1

HCID 9802667N-hydroxy-4-({4-[(5-hydroxy-2-pentynyl)oxy]phenyl}sulfonyl)-2,2-dimethyl-3-thiomorpholine carboxamideYield 207.7%

Reagents, catalysts & solvents 4

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.33 g (0.663 mmol) of 2,2-dimethyl-4-[(4-{[5-(tetrahydro-2H-pyran-2-yloxy-2-pentynyl]oxy}phenyl)sulfonyl]-3-thiomorpholine carboxylic acid (Step 5, Example 243) and 0.108 g (0.796 mmol) of 1-hydroxybenzotriazole in 3 mL of dichloromethane and 1 mL of DMF was added 0.169 g (0.88 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and the reaction was stirred at room temperature for 1 h. Then 0.203 mL (3.31 mmol) of 50% aqueous hydroxylamine was added and the reaction was stirred for 18 h. The reaction was diluted with ethyl acetate, washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was dissolved in 10 mL of methanol and 0.028 g (0.11 mmol) of pyridinium p-toluenesulfonate was added and the reaction was heated to reflux for 18 h. The reaction was concentrated in vacuo and the residue was chromatographed on silica gel eluting with 2.5% MeOH/CH2Cl2 to provide 0.59 g (21%) of N-hydroxy-4-({4-[(5-hydroxy-2-pentynyl)oxy]phenyl}sulfonyl)-2,2-dimethyl-3-thiomorpholine carboxamide as a white solid. Electrospray Mass Spec: 429.1 (M+H)+

Workup

  1. stirringthe reaction was stirred for 18 h
  2. washwashed with water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in 10 mL of methanol
  7. temperaturethe reaction was heated
  8. temperatureto reflux for 18 h
  9. concentrationThe reaction was concentrated in vacuo
  10. customthe residue was chromatographed on silica gel eluting with 2.5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-378b9437b1b9465ba704bc9c72978ad0
Source dataset
uspto-grants-2004_11
Patent number
US06812227B2

Reaction notes

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