Hydroxyamine hydrochloride → HCID 69936625, compound

HRID 2405142Notes

Reaction equation

HRID 2405142 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=O)[CH2:9][O:10][CH:11]([CH:33]=[CH2:34])[CH2:12][O:13][C:14]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([O-])(=O)C.[Na+].Cl.[NH2:42][OH:43]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]12[CH2:9][O:10][CH:11]([CH2:12][O:13][C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:33]1[CH2:34][O:43][NH:42]2

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 70496926HCID 70496926, compound

Product 1

HCID 69936625HCID 69936625, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A reactor was charged with 1-(2-fluorophenyl)-2-((1-(trityloxy)but-3-en-2-yl)oxy)ethanone (61.2 g, 1.0 equiv), toluene (428 mL) and sodium acetate (16.1 g, 1.5 equiv). Upon complete addition, the reaction mixture was stirred at ambient temperature for 5 minutes. Hydroxylamine hydrochloride (10.0 g, 1.1 Eq) was added and the suspension was heated to 111° C. After stirring for >20 hours at 111° C., the reaction mixture was allowed to cool down to ambient temperature, and the suspension was filtered and the solids rinsed with toluene (245 mL) and then THF (10 volumes) The filtrate was concentrated under reduced pressure (bath temp. ≦40° C.) and chased with 2-propanol (275 mL) 2-Propanol (428 mL) was added to the solids and the suspension was heated to 83° C. After stirring for 1 hour at 83° C., the mixture was allowed to cool down to ambient temperature. The slurry was cooled to 0° C. over a 1 hour period and stirred at 0° C. for 1 hour. The suspension was filtered and the solids rinsed in two portions with cold 2-propanol (490 mL) to give 6a-(2-fluorophenyl)-4-((trityloxy)methyl)hexahydrofuro[3,4-c]isoxazole (42.3 g) as a solid.

Workup

  1. additionUpon complete addition
  2. temperaturethe suspension was heated to 111° C
  3. stirringAfter stirring for >20 hours at 111° C.
  4. temperatureto cool down to ambient temperature
  5. filtrationthe suspension was filtered
  6. washthe solids rinsed with toluene (245 mL)
  7. concentrationTHF (10 volumes) The filtrate was concentrated under reduced pressure (bath temp. ≦40° C.) and chased with 2-propanol (275 mL) 2-Propanol (428 mL)
  8. additionwas added to the solids
  9. temperaturethe suspension was heated to 83° C
  10. stirringAfter stirring for 1 hour at 83° C.
  11. temperatureto cool down to ambient temperature
  12. temperatureThe slurry was cooled to 0° C. over a 1 hour period
  13. stirringstirred at 0° C. for 1 hour
  14. filtrationThe suspension was filtered
  15. washthe solids rinsed in two portions with cold 2-propanol (490 mL)

Sources & evidence

ORD record
ord-e91b4aabded0415e840deef8850458dd
Source dataset
uspto-grants-2014_08
Patent number
US08802871B2

Reaction notes

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