Sodium Carbonate → (R)-8-Fluoro-3-hydroxylamino-5-methoxy-3,4-dihydro-2H-1-benzopyran

HRID 52266Notes

Reaction equation

HRID 52266 reaction equation
ClC1C=C(C=CC=1)C(OO)=[O:6].[F:12][C:13]1[C:22]2[O:21][CH2:20][C@H:19]([N:23]=CC3C=CC(OC)=CC=3)[CH2:18][C:17]=2[C:16]([O:33][CH3:34])=[CH:15][CH:14]=1.Cl.NO.C([O-])([O-])=O.[Na+].[Na+]>O.CO.C(Cl)Cl>[F:12][C:13]1[C:22]2[O:21][CH2:20][C@H:19]([NH:23][OH:6])[CH2:18][C:17]=2[C:16]([O:33][CH3:34])=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 70297m-Chloroperbenzoic acidHCID 443297Hydroxyamine hydrochlorideHCID 54028897(R)-8-fluoro-5-methoxy-3-[N-(4-methoxybenzylidene)-amino]-3,4-dihydro-2H-1-benzopyran

Product 1

HCID 22871226(R)-8-Fluoro-3-hydroxylamino-5-methoxy-3,4-dihydro-2H-1-benzopyranYield 89%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

3 -Chloroperoxybenzoic acid (85%; 7.6 g, 37.6 mmol) was added in portions to a stirred and cooled solution (+4° C.) of (R)-8-fluoro-5-methoxy-3-[N-(4-methoxybenzylidene)-amino]-3,4-dihydro-2H-1-benzopyran (10.8 g, 34 mmol) and methylene chloride (65 mL). The mixture was stirred over night at room temperature. Precipitated 3-chlorobenzoic acid was filtered off and the clear yellow filtrate was concentrated in vacuo. The oily residue was taken up in a solution of hydroxylamine hydrochloride (2.83 g, 40.8 mmol) and anhydrous methanol (60 mL) and the resulting solution was stirred at room temperature for 2 h. The solvent was evaporated to give a thick orange oil. Water was added to the oil, pH was adjusted to 8-9 with saturated aqueous Na2CO3 and the mixture was washed with ether (3×150 mL). The organic phases were combined, washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was flash chromatographed on silica with EtOAc (15 to 50%) in hexane as eluent. The resulting impure product was flash chromatographed a second time on silica with EtOH- CHCl3 (1:99) as eluent to give 6.45 g (89% yield) of the title compound as a colourless crystalline solid. Mp: 111°-113° C. [α]21D =+66.4° (C=1.3; CHCl3). GC-MS (70 eV) M=213 (56%).

Workup

  1. stirringThe mixture was stirred over night at room temperature
  2. filtrationPrecipitated 3-chlorobenzoic acid was filtered off
  3. concentrationthe clear yellow filtrate was concentrated in vacuo
  4. stirringthe resulting solution was stirred at room temperature for 2 h
  5. customThe solvent was evaporated
  6. customto give a thick orange oil
  7. washthe mixture was washed with ether (3×150 mL)
  8. washwashed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customchromatographed on silica with EtOAc (15 to 50%) in hexane as eluent
  13. customchromatographed a second time on silica with EtOH- CHCl3 (1:99) as eluent

Sources & evidence

ORD record
ord-f28c25d6fca74cd3998eaac38ea5bc24
Source dataset
uspto-grants-1997_04
Patent number
US05616610

Reaction notes

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