P-Chloroacetophenone → HCID 86722009, compound

HRID 1398046Notes

Reaction equation

HRID 1398046 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[O:21]1[CH2:26][CH2:25][CH:24]([C:27](Cl)=[O:28])[CH2:23][CH2:22]1>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH2:9][C:27]([CH:24]2[CH2:25][CH2:26][O:21][CH2:22][CH2:23]2)=[O:28])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7467P-ChloroacetophenoneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 2795505Oxane-4-carbonyl chloride

Product 1

HCID 86722009HCID 86722009, compoundYield 58.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 1-(4-chlorophenyl)ethanone (2.0 g, 12.9 mmol) in anhydrous THF was cooled in a dry ice acetone bath and treated with sodium hexamethyldisilazid (14.2 mL, 1M in THF, 14.2 mmol). The resulting solution was stirred for 1 h at −78° C. and a solution of tetrahydro-pyran-4-carbonyl chloride (1.92 g, 12.9 mmol) in THF was slowly added. The resulting solution was stirred for 30 min at −78° C., allowed to warm up to room temperature and stirred for 5 h. The reaction was quenched by adding 6N HCl and extracted with EtOAc (×3). The organic fractions were combined and washed with sat. NaCl, dried over Na2SO4 and evaporated under vacuum. The resulting residue was purified by silica column chromatography to give 2 g (58%) of 1-(4-chlorophenyl)-3-(tetrahydro-2H-pyran-4-yl)propane-1,3-dione. 1-(4-chlorophenyl)-3-(tetrahydro-2H-pyran-4-yl)propane-1,3-dione 1 g (3.75 mmol) was taken in absolute ethanol (20 mL) and TEA (1.4 mL, 10 mmol) was added slowly. This solution was stirred for 20 min and added drop-wise to a solution of (2-methoxyphenyl)hydrazine hydrochloride (0.7 g, 4.0 mmol) in ethanol (20 mL). This solution was heated to 60° C. and stirred for 5 h. Ethanol was removed under vacuum and the residue was taken in EtOAc and washed with water, and sat. NaCl. The solution was dried over Na2SO4 and evaporated. The residue was purified by silica column chromatography to give 5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole.

Workup

  1. stirringThe resulting solution was stirred for 30 min at −78° C.
  2. temperatureto warm up to room temperature
  3. stirringstirred for 5 h
  4. customThe reaction was quenched
  5. additionby adding 6N HCl
  6. extractionextracted with EtOAc (×3)
  7. washwashed with sat. NaCl
  8. dry with materialdried over Na2SO4
  9. customevaporated under vacuum
  10. customThe resulting residue was purified by silica column chromatography

Sources & evidence

ORD record
ord-54985ebea3424d88aa0a7f2da45b425e
Source dataset
uspto-grants-2014_12
Patent number
US08901314B2

Reaction notes

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