Sulfuric Acid → N-(2-fluoro-5-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide

HRID 1284613Notes

Reaction equation

HRID 1284613 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](N)=[CH:4][C:3]=1[N:9]1[C:13](=[O:14])[C:12]2[CH2:15][CH2:16][CH2:17][CH2:18][C:11]=2[C:10]1=[O:19].S(=O)(=O)(O)[OH:21].N([O-])=O.[Na+].NC(N)=O>O.C(O)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:21])=[CH:4][C:3]=1[N:9]1[C:13](=[O:14])[C:12]2[CH2:15][CH2:16][CH2:17][CH2:18][C:11]=2[C:10]1=[O:19]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 1176UreaHCID 10332826N-(2-fluoro-5-aminophenyl)-3,4,5,6-tetrahydrophthalimideHCID 23668193Sodium Nitrite2×

Product 1

HCID 13519181N-(2-fluoro-5-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimideYield 26.8%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Procedure

To N-(2-fluoro-5-aminophenyl)-3,4,5,6-tetrahydrophthalimide (VIII) (2.6 g), acetic acid (26 g) and conc. sulfuric acid (2.5 g) were added, and the resultant mixture was kept at a temperature below 10° C. A solution of sodium nitrite (1.0 g) in water (10 g) was added dropwise thereto at a temperature of 5° to 10° C. The resulting mixture was stirred for 15 minutes, followed by decomposition of excess of sodium nitrite with urea (0.3 g). A solution of cupric nitrate (38.6 g) in water (100 g) was added dropwise thereto at room temperature. After addition of cuprous oxide (1.5 g), the resultant mixture was stirred vigorously at room temperature for 10 minutes. The reaction mixture was extracted with ethyl acetate, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel chromatography using a mixture of n-hexane and ethyl acetate as an eluent to give 0.7 g of N-(2-fluoro-5-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide (VI). M.P., 164.6° C. M.P., 164.6° C.

Workup

  1. customwas kept at a temperature below 10° C
  2. customat a temperature of 5° to 10° C
  3. customat room temperature
  4. extractionThe reaction mixture was extracted with ethyl acetate
  5. customthe solvent was removed by distillation under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. additiona mixture of n-hexane and ethyl acetate as an eluent

Sources & evidence

ORD record
ord-11df489102294d3190436f3f2ea77b66
Source dataset
uspto-grants-1986_01
Patent number
US04563535

Reaction notes

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