p-Fluorophenethylamine → (3R*,4S*)-4-{[2-(4-fluorophenyl)ethyl]amino}-2,2-dimethyl-7-nitro-3-chromanol

HRID 505647Notes

Reaction equation

HRID 505647 reaction equation
O1[C@H:11]2[C@:2]1([OH:17])[C:3]([CH3:16])([CH3:15])[O:4][C:5]1[C:10]2=[CH:9][CH:8]=[C:7]([N+:12]([O-:14])=[O:13])[CH:6]=1.Cl([O-])(=O)(=O)=O.[Li+].[F:24][C:25]1[CH:33]=[CH:32][C:28]([CH2:29][CH2:30][NH2:31])=[CH:27][CH:26]=1.C(O)(=O)/C=C\C(O)=O>O1CCOCC1.C(OCC)(=O)C.C(O)C>[F:24][C:25]1[CH:33]=[CH:32][C:28]([CH2:29][CH2:30][NH:31][C@H:11]2[C:10]3[C:5](=[CH:6][C:7]([N+:12]([O-:14])=[O:13])=[CH:8][CH:9]=3)[O:4][C:3]([CH3:15])([CH3:16])[C@@H:2]2[OH:17])=[CH:27][CH:26]=1

Participants

8

Reactant 4

HCID 4653p-FluorophenethylamineHCID 444266Maleic AcidHCID 23665649Lithium perchlorateHCID 86761162(3R*,4R*)-3,4-epoxy-2,2-dimethyl-7-nitro-3-chromanol

Product 1

HCID 59031743(3R*,4S*)-4-{[2-(4-fluorophenyl)ethyl]amino}-2,2-dimethyl-7-nitro-3-chromanolYield 81%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (3R*,4R*)-3,4-epoxy-2,2-dimethyl-7-nitro-3-chromanol (2.07 g, 9.37 mmol) in dioxane (4 mL), lithium perchlorate (997 mg, 9.37 mmol) and 4-fluorophenethyl amine (1.47 mL, 11.3 mmol) were added, and the resulting solution was stirred at 70° C. for 3.5 hours under nitrogen atmosphere. The reaction solution was diluted with ethyl acetate, washed with saturated sodium hydrogen carbonate solution and saturated sodium chloride solution. Then, the organic phase was dried over magnesium sulfate and concentrated under a reduced pressure. The resulting residue was diluted with ethanol, and a solution of maleic acid (1.20 g, 10.3 mmol) in ethanol was added dropwise thereto. The resulting solid was filtered off, and washed with ethyl acetate. The resulting solid was suspended in ethyl acetate, the resulting suspension was neutralized with 1 mol/L sodium hydroxide aqueous solution and washed with saturated sodium chloride solution. After drying the organic phase over magnesium sulfate, it was dried under a reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain (3R*,4S*)-4-{[2-(4-fluorophenyl)ethyl]amino}-2,2-dimethyl-7-nitro-3-chromanol (yield: 81%).

Workup

  1. washwashed with saturated sodium hydrogen carbonate solution and saturated sodium chloride solution
  2. dry with materialThen, the organic phase was dried over magnesium sulfate
  3. concentrationconcentrated under a reduced pressure
  4. additionThe resulting residue was diluted with ethanol
  5. filtrationThe resulting solid was filtered off
  6. washwashed with ethyl acetate
  7. washwashed with saturated sodium chloride solution
  8. dry with materialAfter drying the organic phase over magnesium sulfate, it
  9. customwas dried under a reduced pressure
  10. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-88df2a59d8f14d5d9325b96b4d638b25
Source dataset
uspto-grants-2010_08
Patent number
US07781483B2

Reaction notes

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