Hydroxylamine → 2-{[4-(3-chloro-propoxy)-benzenesulfonyl]-(4-methoxy-benzyl)amino}-N-hydroxy-acetamide

HRID 1662973Notes

Reaction equation

HRID 1662973 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([N:15]([CH2:25][C:26]([OH:28])=O)[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)(=[O:14])=[O:13])=[CH:8][CH:7]=1.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:40][OH:41].N#N>C(Cl)Cl.O.C1COCC1>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([N:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH2:25][C:26]([NH:40][OH:41])=[O:28])(=[O:14])=[O:13])=[CH:8][CH:7]=1

Participants

9

Reactant 5

HCID 787HydroxylamineHCID 947NitrogenHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 21884785{[4-(3-Chloro-propoxy)-benzenesulfonyl]-(4-methoxybenzyl)-amino}-acetic acid

Product 1

HCID 99330622-{[4-(3-chloro-propoxy)-benzenesulfonyl]-(4-methoxy-benzyl)amino}-N-hydroxy-acetamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
2.5 °C

Procedure

To a solution of 48.81 g (0.114 mol) of {[4-(3-chloro-propoxy)-benzenesulfonyl]-(4-methoxybenzyl)-amino}-acetic acid in 500 ml of CH2Cl2, 19.56 ml (0.228 mol) of oxalyl chloride and 0.88 ml (0.011 mol) of DMF are added dropwise at 0-5° C. under N2 atmosphere. The mixture is stirred for 1 h at 0-5° C. and 1 h at r.t. To a solution of 226 ml (3.42 mol) of) 50% hydroxylamine in H2O (Aldrich) in 1200 ml of THF, a solution of the freshly prepared above acid chloride in CH2Cl2 is added over 45 min. at −10 to −5° C. through a teflon tube using N2 gas pressure. The reaction mixture is stirred for 30 min at −5 to 0° C. and filtered through, paper filter to remove insoluble precipitates. The filtrate is diluted with H2O and extracted with CH2Cl2. The combined extracts are washed with brine, dried over MgSO4 and concentrated under reduced pressure. The product is collected by filtration and washed with ether to give 43.03 g of 2-{[4-(3-chloro-propoxy)-benzenesulfonyl]-(4-methoxy-benzyl)amino}-N-hydroxy-acetamide; NMR (CDCl3): 2.2-2.35 (m, 2H), 3.69 (s, 2H), 3.76 (t, 2H, J=6 Hz), 3.79 (s, 3H), 4.21 (t, 2H, J=6 Hz), 4.26 (s, 2H), 6.77 (br s, 1H), 6.85 (d, 2H, J=9.04 Hz), 7.03 (d, 2H, J=9.04 Hz), 7.15 (d, 2H, J=9.04 Hz), 7.78 (d, 2H, J=8.56 Hz), 8.82 (br s, 1H).

Workup

  1. additionis added over 45 min. at −10 to −5° C. through a teflon tube
  2. stirringThe reaction mixture is stirred for 30 min at −5 to 0° C.
  3. filtrationfiltered through, paper
  4. filtrationfilter
  5. customto remove insoluble precipitates
  6. additionThe filtrate is diluted with H2O
  7. extractionextracted with CH2Cl2
  8. washThe combined extracts are washed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated under reduced pressure
  11. filtrationThe product is collected by filtration
  12. washwashed with ether

Sources & evidence

ORD record
ord-486821c0bd084ccb9d7b806c22c4d789
Source dataset
uspto-grants-2011_10
Patent number
US08034810B2

Reaction notes

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