Thionyl Chloride → Ethyl 1-{4-[(4-chloromethyl-2-methoxyphenoxy)methyl]-5-methyl-1,3-thiazol-2-yl}piperidine-4-carboxylate

HRID 2221641Notes

Reaction equation

HRID 2221641 reaction equation
O[CH2:2][C:3]1[CH:27]=[CH:26][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([N:15]3[CH2:20][CH2:19][CH:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:17][CH2:16]3)[S:12][C:13]=2[CH3:14])=[C:5]([O:28][CH3:29])[CH:4]=1.S(Cl)([Cl:32])=O>C1(C)C=CC=CC=1>[Cl:32][CH2:2][C:3]1[CH:27]=[CH:26][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([N:15]3[CH2:20][CH2:19][CH:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:17][CH2:16]3)[S:12][C:13]=2[CH3:14])=[C:5]([O:28][CH3:29])[CH:4]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 69215032Ethyl 1-{4-[(4-hydroxymethyl-2-methoxyphenoxy)methyl]-5-methyl-1,3-thiazol-2-yl}piperidine-4-carboxylate

Product 1

HCID 69217581Ethyl 1-{4-[(4-chloromethyl-2-methoxyphenoxy)methyl]-5-methyl-1,3-thiazol-2-yl}piperidine-4-carboxylateYield 32%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture of ethyl 1-{4-[(4-hydroxymethyl-2-methoxyphenoxy)methyl]-5-methyl-1,3-thiazol-2-yl}piperidine-4-carboxylate (1.35 g) and toluene (50 mL) was added thionyl chloride (0.42 g), and the mixture was heated under reflux for 2 hrs. The reaction mixture was concentrated and ethyl acetate was added to the residue. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:4, v/v) to give ethyl 1-{4-[(4-chloromethyl-2-methoxyphenoxy)methyl]-5-methyl-1,3-thiazol-2-yl}piperidine-4-carboxylate as colorless crystals (0.45 g, yield 32%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 98-99° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hrs
  3. concentrationThe reaction mixture was concentrated
  4. additionethyl acetate was added to the residue
  5. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. washeluted with ethyl acetate-hexane (1:4, v/v)

Sources & evidence

ORD record
ord-f057c547397749ec8efe41f21f1ae62e
Source dataset
uspto-grants-2008_05
Patent number
US07368578B2

Reaction notes

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