Hydrochloric Acid → 4-benzoyl-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide

HRID 422960Notes

Reaction equation

HRID 422960 reaction equation
Cl.[NH2:2][OH:3].C[O-].[Na+].[OH:7][C@H:8]([CH3:31])[C@H:9]([NH:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([C:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:24])=[CH:19][CH:18]=1)=[O:16])[C:10](OC)=[O:11].Cl>CO>[C:23]([C:20]1[CH:21]=[CH:22][C:17]([C:15]([NH:14][C@H:9]([C:10]([NH:2][OH:3])=[O:11])[C@H:8]([OH:7])[CH3:31])=[O:16])=[CH:18][CH:19]=1)(=[O:24])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 443297Hydroxyamine hydrochlorideHCID 10942334Sodium MethoxideHCID 59697585methyl(2S,3R)-3-hydroxy-2-{[4-(phenylcarbonyl)phenyl]carbonylamino}butanoate

Product 1

HCID 596972734-benzoyl-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamideYield 43%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of hydroxylamine hydrochloride (121 mg, 1.74 mmol) in anhydrous MeOH (2.0 mL) at 0° C. under N2 atmosphere was added sodium methoxide (25 wt % in MeOH, 680 mg, 3.14 mmol). A precipitate was immediately observed and the cloudy white solution was stirred for 10 minutes at 0° C. A solution of methyl (2S,3R)-3-hydroxy-2-{[4-(phenylcarbonyl)phenyl]carbonylamino}butanoate (1) (534 mg, 1.56 mmol) in MeOH (3.0 mL) was added and the reaction stirred 3 h at 0° C., then warmed gradually to ambient temperature overnight (18 h total). Aqueous 0.5 M HCl (20 mL) was added and the solution extracted with 5:1 chloroform/isopropyl alcohol (4×40 mL). The organic layers were combined, dried over Na2SO4 and concentrated to give an orange foam. Purification by silica gel chromatography (increasing eluant polarity from 30:1 CH2Cl2/MeOH to 15:1 CH2Cl2/MeOH) afforded 228 mg (43%) of 4-benzoyl-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide.

Workup

  1. stirringthe reaction stirred 3 h at 0° C.
  2. temperaturewarmed gradually to ambient temperature overnight (18 h total)
  3. extractionthe solution extracted with 5:1 chloroform/isopropyl alcohol (4×40 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto give an orange foam
  7. customPurification
  8. temperatureby silica gel chromatography (increasing eluant polarity from 30:1 CH2Cl2/MeOH to 15:1 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-62cf5ba546864d548e6b2f7f444d07f6
Source dataset
uspto-grants-2012_01
Patent number
US08101640B2

Reaction notes

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