Hydrochloric Acid → Hydroxylamine, O-(3,4,5-trimethoxybenzyl)-, hydrochloride

HRID 1663093Notes

Reaction equation

HRID 1663093 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12])[CH2:6][Cl:7].C(OC(=O)[NH:21][OH:22])(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].Cl>C(#N)C.CCOC(C)=O.O>[ClH:7].[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12])[CH2:6][O:22][NH2:21]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 774485-(Chloromethyl)-1,2,3-trimethoxybenzeneHCID 97534tert-butyl N-hydroxycarbamate

Product 1

HCID 200499Hydroxylamine, O-(3,4,5-trimethoxybenzyl)-, hydrochlorideYield 18.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 3,4,5-trimethoxybenzyl chloride (1.00 g, 4.6 mmol) and tert-butyl-N-hydroxycarbamate (0.62 g, 4.6 mmol) in acetonitrile (20 ml) was added Cs2CO3 (4.51 g, 13.8 mmol). The reaction mixture was stirred at room temperature for 24 hours. Water was added and the products extracted twice with EtOAc. The combined organic extracts were washed with water and brine, dried (MgSO4) and evaporated under reduced pressure. The crude product was purified by chromatography on silica using a gradient of EtOAc in petroleum ether (0-40%, v/v) affording 411 mg of Boc-protected O-(3,4,5-trimethoxy-benzyl)-hydroxylamine. This intermediate (383 mg/1.22 mmol) was treated with 37% hydrochloric acid (2.5 ml) in EtOAc (7.5 ml) for 30 min. at room temperature. The mixture was concentrated under reduced pressure and diethyl ether was added. The resulting precipitated material was isolated by filtration and dried under high vacuum affording the title compound (211 mg) as white shiny crystals.

Workup

  1. extractionthe products extracted twice with EtOAc
  2. washThe combined organic extracts were washed with water and brine
  3. dry with materialdried (MgSO4)
  4. customevaporated under reduced pressure
  5. customThe crude product was purified by chromatography on silica using a gradient of EtOAc in petroleum ether (0-40%, v/v)
  6. customaffording 411 mg of Boc-protected O-(3,4,5-trimethoxy-benzyl)-hydroxylamine
  7. concentrationThe mixture was concentrated under reduced pressure and diethyl ether
  8. additionwas added
  9. customThe resulting precipitated material
  10. customwas isolated by filtration
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-3c62157c16e74de3a5cfd03e48b75891
Source dataset
uspto-grants-2011_10
Patent number
US08034811B2

Reaction notes

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