Hydroxylamine → N-hydroxy-4-{2-[5-(2-pyrrolidin-1-ylethyloxy)benzofuran-2-ylcarbonylamino]ethoxy}benzamide

HRID 2111145Notes

Reaction equation

HRID 2111145 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][NH:13][C:14]([C:16]2[O:17][C:18]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)=[CH:21][C:19]=3[CH:20]=2)=[O:15])=[CH:6][CH:5]=1.[NH2:34][OH:35].[OH-].[Na+]>CO.O1CCCC1.O>[OH:35][NH:34][C:3](=[O:2])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][NH:13][C:14]([C:16]2[O:17][C:18]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]4[CH2:29][CH2:30][CH2:31][CH2:32]4)=[CH:21][C:19]=3[CH:20]=2)=[O:15])=[CH:6][CH:5]=1

Participants

7

Reactant 3

HCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 666881644-{2-[5-(2-Pyrrolidin-1-ylethoxy)benzofuran-2-carbonylamino]-ethoxy}-benzoic acid methyl ester

Product 1

HCID 9846722N-hydroxy-4-{2-[5-(2-pyrrolidin-1-ylethyloxy)benzofuran-2-ylcarbonylamino]ethoxy}benzamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-{2-[5-(2-pyrrolidin-1-ylethoxy)benzofuran-2-carbonylamino]-ethoxy}-benzoic acid methyl ester (169 mg, 0.37 mmol) in methanol (8 ml) and tetrahydrofuran (4 ml) was added hydroxylamine in water (2.9 ml of a 50 wt. % solution) and 4.0 M aqueous solution of sodium hydroxide (0.65 ml). After stirring for 18 h, the organics were removed and the aqueous solution was cooled in an ice/water bath and the pH was adjusted to ˜8 with 4.4 ml 1.0 M hydrochloric acid to give precipitates. The heterogeneous solution was warmed to room temperature and acetonitrile was added till the precipitates dissolved. The solution was chromatographed on C-18 reverse phase HPLC. Fractions with absorbance at 214 nm, were collected, frozen, and lyophilize to give the title compound (31 mg). 1H NMR (400 MHz, DMSO-d6) δ: 11.05 (s, 1H), 10.4 (s, 1H), 8.91 (s, 2H), 7.70 (d, 2H, J=7.4), 7.59 (dd, 1H, J=3.7, 9.1 Hz), 7.51 (d, 1H, J=3.7 Hz), 7.35 (s, 1H), 7.13 (d, 1H, J=9.0 Hz), 7.00 (d, 2H, J=7.4 Hz), 4.37 (m, 2H), 4.18 (m, 2H), 3.62 (m, 6H), 3.12 (m, 2H), 2.02 (m, 2H), 1.89 (m, 2H). EM (calc.): 453.2; MS (ESI) m/e (M+1H)+: 454.1, (M−1H)−: 452.2.

Workup

  1. customthe organics were removed
  2. temperaturethe aqueous solution was cooled in an ice/water bath
  3. customto give
  4. customprecipitates
  5. additionacetonitrile was added till the precipitates
  6. dissolutiondissolved
  7. customThe solution was chromatographed on C-18 reverse phase HPLC
  8. customFractions with absorbance at 214 nm, were collected
  9. temperaturefrozen

Sources & evidence

ORD record
ord-c3115b1f92dd431da8908c12b5199f97
Source dataset
uspto-grants-2009_04
Patent number
US07517988B2

Reaction notes

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