HCID 56947871, compound → HCID 56948114, compound

HRID 572835Notes

Reaction equation

HRID 572835 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([O:25][CH:26]1[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]1)[C:11]1[CH:12]=[C:13](OS(C(F)(F)F)(=O)=O)[CH:14]=[CH:15][CH:16]=1.[CH2:33]([Mg]Cl)[CH2:34][CH2:35][CH3:36]>O1CCCC1.CN1CCCC1=O.C(OCC)C>[CH2:33]([C:13]1[CH:12]=[C:11]([CH:10]([O:25][CH:26]2[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]2)[C:2]2[S:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)[CH:16]=[CH:15][CH:14]=1)[CH2:34][CH2:35][CH3:36]

Participants

6

Reactant 2

HCID 56947871HCID 56947871, compoundHCID 178418265HCID 178418265, compound2×

Product 1

HCID 56948114HCID 56948114, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of trifluoromethanesulfonic acid 3-[benzothiazol-2-yl(1-methylpiperidin-4-yloxy)methyl]phenyl ester (110 mg) and ferric acetylacetonate (4 mg) in a mixture of tetrahydrofurane (4.5 mL) and N-methylpyrrolidone (0.25 mL) cooled at 0° C. is added a 2M solution of butylmagnesium chloride in tetrahydrofurane (150 μL). The mixture is stirred at room temperature for 25 min, then warmed at 30° C. for 15 min. A second addition of butylmagnesium chloride in tetrahydrofurane (150 μL) is performed. The mixture is then diluted with diethyl ether and quenched with 0.5N hydrochloric solution. The aqueous phase is extracted with diethyl ether, then ethyl acetate. Organic phases are pooled, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography (gradient heptane/ethyl acetate from 99/1 to 90/10). The product is then refluxed in methanol and concentrated to give 2-[(3-butylphenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole.

Workup

  1. temperaturewarmed at 30° C. for 15 min
  2. customquenched with 0.5N hydrochloric solution
  3. extractionThe aqueous phase is extracted with diethyl ether
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by chromatography (gradient heptane/ethyl acetate from 99/1 to 90/10)
  7. temperatureThe product is then refluxed in methanol
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-780a03d64a8e4de3bf5a863486241212
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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