Hydrochloric Acid → HCID 23368429, compound

HRID 1901614Notes

Reaction equation

HRID 1901614 reaction equation
[NH2:1][CH:2]([CH2:15][O:16][CH3:17])[CH2:3][O:4][C:5]1[C:9]2[CH:10]=[C:11]([Cl:14])[CH:12]=[CH:13][C:8]=2[O:7][N:6]=1.[C:18]([C:22]1[CH:23]=[C:24]([CH:27]=[C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])[C:29]=1[OH:30])[CH:25]=O)([CH3:21])([CH3:20])[CH3:19].C1(C)C=CC(S(O)(=O)=O)=CC=1.C([BH3-])#N.[Na+].[OH-].[Na+].Cl>CO.C(OCC)C.O1CCOCC1.O.C(OCC)(=O)C>[ClH:14].[C:31]([C:28]1[CH:27]=[C:24]([CH:23]=[C:22]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:29]=1[OH:30])[CH2:25][NH:1][CH:2]([CH2:15][O:16][CH3:17])[CH2:3][O:4][C:5]1[C:9]2[CH:10]=[C:11]([Cl:14])[CH:12]=[CH:13][C:8]=2[O:7][N:6]=1)([CH3:33])([CH3:34])[CH3:32]

Participants

12

Reactant 6

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 14798Sodium HydroxideHCID 732193,5-Di-tert-butyl-4-hydroxybenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 23368365HCID 23368365, compound

Product 1

HCID 23368429HCID 23368429, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 0.50 g of 3-(2-amino-3-methoxypropoxy)-5-chloro-1,2-benzoisoxazole and 0.5 g of 3,5-di-tert-butyl-4-hydroxybenzaldehyde in 5 ml of methanol is added 0.41 g of p-toluenesulfonic acid at 20°-25° C., and they are subjected to reaction at the same temperature for one hour. Subsequently, 0.13 g of sodium cyanoborohydride is added at 20°-25° C., and they are subjected to reaction at the same temperature overnight. Water and ethyl acetate are added to the reaction mixture and the pH is adjusted to 10 with a 10% (w/w) aqueous sodium hydroxide solution, after which the organic layer is separated. The separated organic layer is washed with a saturated saline solution and dried over anhydrous magnesium sulfate, after which the solvent is removed by distillation under reduced pressure. The residue obtained is purified by a column chromatography [eluant:n-hexane:ethyl acetate=5:1], to obtain an oily product. The oily product obtained is dissolved in 10 ml of diethyl ether and 1 ml of water and to this solution is added 0.58 ml of a dioxane solution (2.2N) of hydrogen chloride, after which the crystals precipitated are collected by filtration and recrystallized from 50% ethanol, to obtain 0.27 g of colorless, crystalline 3-[2-(3,5-di-tert-butyl-4-hydroxybenzyl)amino-3-methoxypropoxy]-5-chloro-1,2-benzoisoxazole hydrochloride having a melting point of 191°-192° C.

Workup

  1. customthey are subjected to reaction at the same temperature for one hour
  2. customthey are subjected to reaction at the same temperature overnight
  3. customafter which the organic layer is separated
  4. washThe separated organic layer is washed with a saturated saline solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customafter which the solvent is removed by distillation under reduced pressure
  7. customThe residue obtained
  8. customis purified by a column chromatography [eluant:n-hexane:ethyl acetate=5:1]
  9. customto obtain an oily product
  10. customThe oily product obtained
  11. customafter which the crystals precipitated
  12. filtrationare collected by filtration
  13. customrecrystallized from 50% ethanol

Sources & evidence

ORD record
ord-55bcecd72f584cb4bd86b3f4a78f78e9
Source dataset
uspto-grants-1996_11
Patent number
US05578627

Reaction notes

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