Hydrochloric Acid → 3-chloro-4-{(E)-2-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-3-yl]vinyl}bicyclo[4.2.1]non-3-en-9-one

HRID 271304Notes

Reaction equation

HRID 271304 reaction equation
Cl.[Cl:2][C:3]1[CH2:10][CH:9]2[C:11]3(OCC[O:12]3)[CH:6]([CH2:7][CH2:8]2)[CH2:5][C:4]=1/[CH:16]=[CH:17]/[C:18]1[CH:22]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[N:20]([CH3:30])[N:19]=1.C(=O)([O-])O.[Na+]>C1COCC1>[Cl:2][C:3]1[CH2:10][CH:9]2[C:11](=[O:12])[CH:6]([CH2:5][C:4]=1/[CH:16]=[CH:17]/[C:18]1[CH:22]=[C:21]([C:23]3[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=3)[N:20]([CH3:30])[N:19]=1)[CH2:7][CH2:8]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 693065173-{(E)-2-[4-chlorospiro[bicyclo[4.2.1]non-3-ene-9,2'-[1,3]dioxolan]-3-yl]vinyl}-5-(4-fluorophenyl)-1-methyl-1H-pyrazole

Product 1

HCID 693100833-chloro-4-{(E)-2-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-3-yl]vinyl}bicyclo[4.2.1]non-3-en-9-oneYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2N hydrochloric acid (100 ml) and the product of Step 2 (18.0 g, 43 mmol) in THF (100 ml) was stirred at 60° C. for 2 hrs. The reaction mixture was basified with saturated sodium hydrogen carbonate and then extracted with ethyl acetate (3×200 ml). The organic extract was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography eluting with ethylacetate: hexane (1:1) to afford 3-chloro-4-{(E)-2-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-3-yl]vinyl}bicyclo[4.2.1]non-3-en-9-one (14.96 g, 94%). δH (400 MHz, CDCl3) 1.59-1.71 (2H, m), 1.76-1.83 (1H, m), 2.02-2.10 (2H, m), 2.38-2.51 (2H, m), 2.58-2.62 (1H, m), 2.87-2.90 (1H, m), 2.96-3.01 (1H, m), 3.84 (3H, s), 6.49 (1H, s), 6.64 (1H, d, J 16.5), 7.14-7.18 (2H, m), 7.38-7.42 (2H, m), 7.54 (1H, d, J 16.5).

Workup

  1. extractionextracted with ethyl acetate (3×200 ml)
  2. extractionThe organic extract
  3. washwas washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography
  7. washeluting with ethylacetate: hexane (1:1)

Sources & evidence

ORD record
ord-4b94b48118254152a5fcdac3e3262050
Source dataset
uspto-grants-2008_11
Patent number
US07452899B2

Reaction notes

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