Phosphorus oxychloride → 3-chloro-2N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-4,5,6,7-tetrahydro-2H-indazole

HRID 21469Notes

Reaction equation

HRID 21469 reaction equation
P(Cl)(Cl)([Cl:3])=O.[F:6][C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([O:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:9][C:8]=1[N:20]1[C:28]2[CH2:27][CH2:26][CH2:25][CH2:24][C:23]=2[C:22](=O)[NH:21]1>[OH-].[Na+]>[Cl:3][C:28]1[N:20]([C:8]2[CH:9]=[C:10]([O:14][CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:11]([Cl:13])=[CH:12][C:7]=2[F:6])[N:21]=[C:22]2[C:27]=1[CH2:26][CH2:25][CH2:24][CH2:23]2

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 86748708(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-one

Product 1

HCID 152793983-chloro-2N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-4,5,6,7-tetrahydro-2H-indazoleYield 26.5%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
160 °C

Procedure

Phosphorus oxychloride (6.6 g, 43.0 mmol) was added to the resulting 2N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-one (15.0 g, 42.8 mmol), followed by stirring for 30 minutes while heating at 160° C. After cooling the reaction solution, an ice-cooled dilute aqueous solution of sodium hydroxide (50 ml) was added thereto, and the mixture was extracted with methylene chloride (200 ml×4). The extract was washed with a dilute aqueous sodium hydroxide (400 ml) and a saturated aqueous solution of sodium chloride (400 ml), and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (development solvent: ethyl acetate/hexane=1/9-1/5) to obtain 3-chloro-2N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-4,5,6,7-tetrahydro-2H-indazole as a white solid (4.3 g 26.5% yield).

Workup

  1. temperatureAfter cooling the reaction solution
  2. additionwas added
  3. extractionthe mixture was extracted with methylene chloride (200 ml×4)
  4. washThe extract was washed with a dilute aqueous sodium hydroxide (400 ml)
  5. dry with materiala saturated aqueous solution of sodium chloride (400 ml), and dried over anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (development solvent: ethyl acetate/hexane=1/9-1/5)

Sources & evidence

ORD record
ord-1f26609fb319468eadc2ce3dbb8082be
Source dataset
uspto-grants-1995_06
Patent number
US05424277

Reaction notes

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