Thionyl Chloride → HCID 15813207, compound

HRID 260714Notes

Reaction equation

HRID 260714 reaction equation
O[C:2]1([CH3:28])[CH:7]([C:8]([O:10][CH3:11])=[O:9])[CH:6]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[C:5]([C:22]([O:24][CH3:25])=[O:23])=[C:4]([NH:26][CH3:27])[CH2:3]1.S(Cl)(Cl)=O>N1C=CC=CC=1>[CH3:28][C:2]1[CH:7]([C:8]([O:10][CH3:11])=[O:9])[CH:6]([C:12]2[CH:13]=[CH:14][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:16][CH:17]=2)[C:5]([C:22]([O:24][CH3:25])=[O:23])=[C:4]([NH:26][CH3:27])[CH:3]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 15813205HCID 15813205, compound

Product 1

HCID 15813207HCID 15813207, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
60 °C

Procedure

10.0 g (25 mmol) of dimethyl 6-hydroxy-6-methyl-4-methylamino-2-(4-trifluoromethylphenyl)-cyclohex-3-ene-1,3-dicarboxylate (preparation analogous to Example II) are heated to 60° C. in 100 ml of pyridine and treated with 2.5 ml of thionyl chloride. The mixture is stirred at 60° C. for 10 minutes and concentrated, and the residue is taken up in methylene chloride, washed three times with water, dried and concentrated. The residue is grossly purified on 200 g of silica gel (petroleum ether/AcOEt=3:1) and then separated by MPLC (methylene chloride/AcOEt=30:1). Two fractions are obtained. 224 mg (2.3%) of dimethyl 4-methyl-6-methylamino-2-(4-trifluoromethylphenyl)-cyclohexa-3,6-diene-1,3-dicarboxylate (non-polar isomer (2)) crystallize from ether/petroleum ether. From the 2nd fraction, 2.29 g (22%) of the polar isomer, dimethyl 6-methyl-4-methylamino-2-(4-trifluoromethylphenyl)-cyclohexa-3,5-diene-1,3-dicarboxylate (3) are precipitated from AcOEt as the hydrochloride (Rf =0.47 (c)).

Workup

  1. concentrationconcentrated
  2. washwashed three times with water
  3. customdried
  4. concentrationconcentrated
  5. customThe residue is grossly purified on 200 g of silica gel (petroleum ether/AcOEt=3:1)
  6. customseparated by MPLC (methylene chloride/AcOEt=30:1)
  7. customTwo fractions are obtained
  8. custom224 mg (2.3%) of dimethyl 4-methyl-6-methylamino-2-(4-trifluoromethylphenyl)-cyclohexa-3,6-diene-1,3-dicarboxylate (non-polar isomer (2)) crystallize from ether/petroleum ether
  9. customFrom the 2nd fraction, 2.29 g (22%) of the polar isomer, dimethyl 6-methyl-4-methylamino-2-(4-trifluoromethylphenyl)-cyclohexa-3,5-diene-1,3-dicarboxylate (3) are precipitated from AcOEt as the hydrochloride (Rf =0.47 (c))

Sources & evidence

ORD record
ord-1aa404fd0ce249a6a3decfecaa0a2642
Source dataset
uspto-grants-1996_06
Patent number
US05530014

Reaction notes

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