N,O-Dimethylhydroxylamine → 4-hydroxy-N-methoxy-N-methyl-3-(morpholinomethyl)benzamide

HRID 2390547Notes

Reaction equation

HRID 2390547 reaction equation
CCN=C=NCCCN(C)C.[OH:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][C:14]=1[CH2:22][N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.[CH3:29][NH:30][O:31][CH3:32].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O>[OH:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([N:30]([O:31][CH3:32])[CH3:29])=[O:19])=[CH:15][C:14]=1[CH2:22][N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1

Participants

8

Reactant 5

HCID 14232N,O-DimethylhydroxylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 41378034-Hydroxy-3-(morpholin-4-ylmethyl)benzoic acid

Product 1

HCID 866390694-hydroxy-N-methoxy-N-methyl-3-(morpholinomethyl)benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

EDCI (4.44 g, 23.18 mmol) was added portionwise to a solution of 4-hydroxy-3-(morpholinomethyl)benzoic acid (5 g, 21.07 mmol), N,O-dimethylhydroxylamine (2.67 g, 27.40 mmol), DIPEA (4.05 mL, 23.18 mmol) and HOBt (3.55 g, 23.18 mmol) in DMF (25 mL) whilst maintaining the temperature below 10° C. The mixture was stirred for 48 h, diluted with EtOAc (200 mL), washed with saturated NaHCO3 (200 mL), water (2×100 mL) & brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by chromatography on silica with EtOAc as eluent to give the sub-title compound as a colourless oil. Yield: 3.20 g

Workup

  1. temperaturewhilst maintaining the temperature below 10° C
  2. washwashed with saturated NaHCO3 (200 mL), water (2×100 mL) & brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was purified by chromatography on silica with EtOAc as eluent

Sources & evidence

ORD record
ord-ac7e0dd124274787801989c372a223e4
Source dataset
uspto-grants-2012_09
Patent number
US08273774B2

Reaction notes

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