Hydroxyamine hydrochloride → HCID 89443940, compound

HRID 526002Notes

Reaction equation

HRID 526002 reaction equation
[C:1](=O)(O)[O-].[Na+].Cl.[NH2:7][OH:8].[C:9]([C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:18](=[O:24])[CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[N:15][CH:16]=1)#[N:10]>O.CO>[OH:8]/[N:7]=[C:9](/[C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:18](=[O:24])[CH2:19][CH2:20][C:21]([O:23][CH3:1])=[O:22])=[N:15][CH:16]=1)\[NH2:10]

Participants

6

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 89449968HCID 89449968, compound

Product 1

HCID 89443940HCID 89443940, compoundYield 40.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A solution of sodium bicarbonate (1.81 g, 21.4 mmol, 5 equiv.) and hydroxylamine hydrochloride (1.50 g, 21.4 mmol, 5 equiv.) in water (12 mL) was added to an solution of 4-[(5-cyano-2-pyridyl)amino]-4-oxo-butanoic acid A2 (1.00 g, 4.29 mmol, 1 equiv.) in methanol (120 mL) at 80° C. The solution was heated at 80° C. overnight, before being concentrated under vacuum. The residue was partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was separated and extracted with ethyl acetate (3×50 ml). The combined organic layer was dried on magnesium sulfate, and then concentrated under vacuum to give 760 mg of crude product. This crude product was adsorbed over isolute before purification by flash chromatography eluted with a gradient of methanol and dichloromethane (0 to 10% in methanol) to give methyl 4-[[5-[(Z)—N′-hydroxycarbamimidoyl]-2-pyridyl]amino]-4-oxo-butanoate (0.46 g, 1.73 mmol, 40% yield).

Workup

  1. concentrationbefore being concentrated under vacuum
  2. customThe residue was partitioned between ethyl acetate (50 mL) and water (50 mL)
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (3×50 ml)
  5. customThe combined organic layer was dried on magnesium sulfate
  6. concentrationconcentrated under vacuum
  7. customto give 760 mg of crude product
  8. customisolute before purification by flash chromatography
  9. washeluted with a gradient of methanol and dichloromethane (0 to 10% in methanol)

Sources & evidence

ORD record
ord-99e94b8acde94968a14cca22fe2c1fbf
Source dataset
uspto-grants-2016_05
Patent number
US09345244B2

Reaction notes

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