Tetrahydrofuran → N-[4-chloro-2-fluoro-5-(methylcarbonyloxymethyl)phenyl]-3,4,5,6-tetrahydrophthalimide

HRID 231431Notes

Reaction equation

HRID 231431 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([F:10])[C:7]([NH2:11])=[CH:6][C:3]=1[CH2:4][OH:5].[C:12]1(=[O:22])[O:17][C:15](=O)[CH:14]2[CH2:18][CH2:19][CH:20]=[CH:21][CH:13]12.[O:23]1CC[CH2:25][CH2:24]1>C(O)(=O)C>[Cl:1][C:2]1[C:3]([CH2:4][O:5][C:24]([CH3:25])=[O:23])=[CH:6][C:7]([N:11]2[C:12](=[O:22])[C:13]3[CH2:21][CH2:20][CH2:19][CH2:18][C:14]=3[C:15]2=[O:17])=[C:8]([F:10])[CH:9]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 127266013a,4,5,7a-Tetrahydro-2-benzofuran-1,3-dioneHCID 13629753(5-Amino-2-chloro-4-fluorophenyl)methanol

Product 1

HCID 20032366N-[4-chloro-2-fluoro-5-(methylcarbonyloxymethyl)phenyl]-3,4,5,6-tetrahydrophthalimide

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4.9 g (0.028 mole) of 2-chloro-4-fluoro-5-aminobenzyl alcohol, 4.25 g (0.028 mole) of tetrahydrophthalic anhydride, and 100 ml of tetrahydrofuran was refluxed overnight. The solvent was evaporated under reduced pressure, leaving a thick, black oil. To this residue was added 100 ml of acetic acid, and the mixture was heated at 100° C. for several hours. The solvent was evaporated under reduced pressure and was replaced with 200 ml of ethyl acetate. This solution was washed three times with 150 ml of a saturated, aqueous solution of sodium bicarbonate and three times with 150 ml of 10% hydrochloric acid. The solution was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure, leaving 8.80 g of a viscous, black oil. This oil was passed through a column of silica gel, eluting with ethyl acetate/heptane (7/13). The appropriate fractions were combined, and the solvent was evaporated under reduced pressure, yielding 6.3 g of N-[4-chloro-2-fluoro- 5-(methylcarbonyloxymethyl)phenyl]-3,4,5,6-tetrahydrophthalimide as a thick, amber oil. The nmr and ir spectra were consistent with the proposed structure.

Workup

  1. temperaturewas refluxed overnight
  2. customThe solvent was evaporated under reduced pressure
  3. customleaving a thick, black oil
  4. customThe solvent was evaporated under reduced pressure
  5. washThis solution was washed three times with 150 ml of a saturated, aqueous solution of sodium bicarbonate and three times with 150 ml of 10% hydrochloric acid
  6. dry with materialThe solution was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. customleaving 8.80 g of a viscous, black oil
  10. washeluting with ethyl acetate/heptane (7/13)
  11. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-39149574a7d94a3782e3d6e3f7254a0b
Source dataset
uspto-grants-1989_07
Patent number
US04846882

Reaction notes

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