Sodium Hydroxide → 3-[N-(N-benzyloxycarbonylaminoacetyl)N-hydroxyamino]propylphosphonic acid

HRID 2051993

Reaction equation

HRID 2051993 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13](Cl)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:16][NH:17][CH2:18][CH2:19][CH2:20][P:21](=[O:24])([OH:23])[OH:22].C(=O)(O)[O-].[Na+].[OH-].[Na+]>C(OCC)C.O.CO>[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13]([N:17]([CH2:18][CH2:19][CH2:20][P:21](=[O:22])([OH:24])[OH:23])[OH:16])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 3421703-(Hydroxyamino)propylphosphonic acidHCID 516892Sodium Bicarbonate2×HCID 12239759Benzyloxycarbonylaminoacetyl chloride

Product 1

HCID 539241393-[N-(N-benzyloxycarbonylaminoacetyl)N-hydroxyamino]propylphosphonic acidYield 32.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of N-benzyloxycarbonylaminoacetyl chloride (2.85 g) in ethyl ether (5 ml) was added dropwise to a solution of 3-(N-hydroxyamino)propylphosphonic acid (985 mg) and sodium bicarbonate (1.51 g) in a mixture of water (20 ml) and methanol (20 ml) with stirring under ice-cooling. During the period, the reaction mixture was adjusted to pH 7-8 with 5% aqueous sodium bicarbonate solution. The stirring was continued for an hour, whereafter the mixture was adjusted to pH 10 with 1 N aqueous sodium hydroxide solution and stirred at the same temperature for 45 minutes. The resultant mixture was adjusted to pH 7 and methanol was distilled off under reduced pressure. The resultant aqueous solution was adjusted to pH 2 with 10% hydrochloric acid and washed with ethyl acetate (30 ml), whereafter the solution was adjusted to pH 1 with 10% hydrochloric acid and then extracted twice with n-butanol (30 ml). The combined n-butanol layer was concentrated under reduced pressure to give a residue, which was crystallized from ether to give 3-[N-(N-benzyloxycarbonylaminoacetyl)N-hydroxyamino]propylphosphonic acid (720 mg) in the form of crystals MP: 101°~105° C.

Workup

  1. temperaturecooling
  2. waitThe stirring was continued for an hour, whereafter the mixture
  3. stirringstirred at the same temperature for 45 minutes
  4. distillationwas distilled off under reduced pressure
  5. washwashed with ethyl acetate (30 ml), whereafter the solution
  6. extractionextracted twice with n-butanol (30 ml)
  7. concentrationThe combined n-butanol layer was concentrated under reduced pressure
  8. customto give a residue, which
  9. customwas crystallized from ether

Sources & evidence

ORD record
ord-9a4bdadb52bf48bdb77c11c1ada89867
Source dataset
uspto-grants-1980_01
Patent number
US04182758

Linked notes

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