Hydroxyamine hydrochloride → tert-butyl 1-(3-chloro-4-(N'-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate

HRID 1804517Notes

Reaction equation

HRID 1804517 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[C:20]#[N:21])[CH2:5][N:6]1[CH2:9][CH:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]1.Cl.[NH2:23][OH:24].C(=O)(O)[O-].[Na+]>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[C:20](=[N:23][OH:24])[NH2:21])[CH2:5][N:6]1[CH2:9][CH:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]1

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochloride2×HCID 516892Sodium Bicarbonate2×HCID 58537201Tert-butyl 1-(3-chloro-4-cyanobenzyl)azetidine-3-carboxylate

Product 1

HCID 76816489tert-butyl 1-(3-chloro-4-(N'-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylateYield 96.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of tert-butyl 1-(3-chloro-4-cyanobenzyl)azetidine-3-carboxylate (0.133 g, 0.434 mmol) in isopropanol (1.2 mL) with hydroxylamine hydrochloride (0.060 g, 0.868 mmol) and sodium bicarbonate (0.146 g, 1.74 mmol) was stirred at 90° C. for 6.5 hrs. HPLC and LCMS indicated the reaction was only 33% complete after 20 minutes. Additional hydroxylamine hydrochloride (0.060 g) and sodium bicarbonate (0.146 g) were added and heating was continued for 5 hrs. The isopropanol was removed under reduced pressure, and the reaction mixture was diluted with ethyl acetate and washed with water (2×), washed with brine, and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded tert-butyl 1-(3-chloro-4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (142 mg) of a tan viscous taffy. The compound had an HPLC ret. time=0.795 min.−Column. PHENOMENEX® S5 4.6×30 mm (2 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=340.11.

Workup

  1. customcomplete after 20 minutes
  2. temperatureheating
  3. customThe isopropanol was removed under reduced pressure
  4. additionthe reaction mixture was diluted with ethyl acetate
  5. washwashed with water (2×)
  6. washwashed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-657dedfa903c48c88fcb1beef667e462
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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