2-[(6-Amino-2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone → 2-[(2-Chloro-6-hydrazinophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone hydrochloride

HRID 2308901Notes

Reaction equation

HRID 2308901 reaction equation
[NH2:1][C:2]1[C:7]([CH2:8][N:9]2[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[CH2:11][O:10]2)=[C:6]([Cl:17])[CH:5]=[CH:4][CH:3]=1.[N:18]([O-])=O.[Na+]>O.Cl>[ClH:17].[Cl:17][C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([NH:1][NH2:18])[C:7]=1[CH2:8][N:9]1[C:13](=[O:14])[C:12]([CH3:15])([CH3:16])[CH2:11][O:10]1

Participants

5

Reactant 2

HCID 139349452-[(6-Amino-2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinoneHCID 23668193Sodium Nitrite

Product 1

HCID 139349472-[(2-Chloro-6-hydrazinophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone hydrochlorideYield 61.9%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of concentrated hydrochloric acid (50 ml) was added 2-[(6-amino-2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone (4.9 g, 0.019 mole). The reaction mixture was cooled to 0° C., and a solution of sodium nitrite (1.3 g, 0.019 mole) in water (20 ml) was added dropwise, with the tip of the addition funnel below the surface of solution. Upon completion of addition, the reaction mixture was stirred at 0° C. for 30 minutes. A solution of stannous chloride dihydrate (9.5 g, 0.042 mole) in concentrated hydrochloric acid (30 ml) was then added dropwise. Upon completion of addition, the reaction mixture was stirred at 0° C. for one hour, after which time an insoluble material was removed by filtration. Ethyl acetate was added to the filtrate and more insoluble material was removed. The ethyl acetate mixture was concentrated under reduced pressure, made basic with aqueous sodium hydroxide, and extracted with methylene chloride. The methylene chloride extract was concentrated under reduced pressure. Concentrated hydrochloric acid was added to the residue and the mixture was concentrated under reduced pressure to yield 1.8 g of 2-[(2-chloro-6-hydrazinophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone hydrochloride as a yellow solid; m.p. 180°-184° C. (dec). The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. additionUpon completion of addition
  3. stirringthe reaction mixture was stirred at 0° C. for one hour
  4. customafter which time an insoluble material was removed by filtration
  5. additionEthyl acetate was added to the filtrate and more insoluble material
  6. customwas removed
  7. concentrationThe ethyl acetate mixture was concentrated under reduced pressure
  8. extractionextracted with methylene chloride
  9. extractionThe methylene chloride extract
  10. concentrationwas concentrated under reduced pressure
  11. additionConcentrated hydrochloric acid was added to the residue
  12. concentrationthe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-882653645d804bb58e8aaa6021238667
Source dataset
uspto-grants-1987_09
Patent number
US04692182

Reaction notes

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