Hydroxylamine → Oxametacin

HRID 1263075Notes

Reaction equation

HRID 1263075 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH2:19][C:20](O)=[O:21])=[C:9]2[CH3:23])=[O:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.C(Cl)(=O)OCC.[NH2:39][OH:40]>C(Cl)(Cl)Cl.O>[CH3:23][C:9]1[N:8]([C:6]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:25][CH:24]=2)=[O:7])[C:16]2[CH:15]=[CH:14][C:13]([O:17][CH3:18])=[CH:12][C:11]=2[C:10]=1[CH2:19][C:20]([NH:39][OH:40])=[O:21]

Participants

7

Reactant 4

HCID 787HydroxylamineHCID 3715IndomethacinHCID 8471TriethylamineHCID 10928Ethyl chloroformate

Product 1

HCID 33675OxametacinYield 88.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

Procedure

In a four-necked flask equipped with a mechanical stirrer, a dropping funnel, a cooler with CaCl2 tube and thermometer, there was poured a solution of 230 g (0.637 mole) of 1-(4-chloro-benzoyl)-5-methoxy-2-methyl-3-indolyl-acetic acid and 88.2 ml (0.637 mole) of triethylamine in 400 ml of chloroform. This solution was added dropwise with stirring to a solution of 60.7 ml (0.637 mole) of ethyl chlorocarbonate, keeping the temperature low by an external cooling of ice and water. The formed triethylamine hydrochloride was removed by filtration, then the chloroform solution was added at room temperature to 21.12 g (0.64 mole) of hydroxylamine. After stirring for some hours, the formed precipitate was recovered by filtration, washed with chloroform, dried and subsequently washed several times with water in order to remove the inorganic residues. After drying in oven, 210 g (yield 91% by weight) of pure oxamethacin were obtained. M.p. 181°-83° C.

Workup

  1. customIn a four-necked flask equipped with a mechanical stirrer, a dropping funnel
  2. additionThis solution was added dropwise
  3. customThe formed triethylamine hydrochloride was removed by filtration
  4. filtrationthe formed precipitate was recovered by filtration
  5. washwashed with chloroform
  6. customdried
  7. customsubsequently washed several times with water in order to remove the inorganic residues
  8. customAfter drying in oven

Sources & evidence

ORD record
ord-325ca1bd78da482ab8d8a1a6c3e7e8ae
Source dataset
uspto-grants-1984_06
Patent number
US04455432

Reaction notes

Loading…