Ethylene Glycol → {3-[Benzothiazol-2-yl(1-methylpiperidin-4-yloxy)methyl]phenyl}benzyl-amine

HRID 572854Notes

Reaction equation

HRID 572854 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:8]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[C:9]2[S:10][C:11]3[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=3[N:13]=2)[CH:5]=[CH:6][CH:7]=1.C(O)CO.C(=O)([O-])[O-].[K+].[K+].[CH2:36]([NH2:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>[Cu]I.CC(O)C>[S:10]1[C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[N:13]=[C:9]1[CH:8]([O:18][CH:19]1[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]1)[C:4]1[CH:3]=[C:2]([NH:43][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 7504BenzylamineHCID 11430Potassium CarbonateHCID 569474582-[(3-Iodophenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole

Product 1

HCID 66835789{3-[Benzothiazol-2-yl(1-methylpiperidin-4-yloxy)methyl]phenyl}benzyl-amine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A screw-capped tube is charged with 2-[(3-iodophenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole (example 41, 190 mg), copper(I) iodide (4 mg), ethylene glycol (45 μL), potassium carbonate (173 mg), benzylamine (54 μL), and propan-2-ol (1 mL). The tube is evacuated, filled with argon and sealed. After stirring at 80° C. for 15 h, the mixture is diluted with ethyl acetate and water and the aqueous phase is extracted with ethyl acetate. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5). The base is converted into its dioxalate salt in acetone to give {3-[benzothiazol-2-yl(1-methylpiperidin-4-yloxy)methyl]phenyl}benzyl-amine, dioxalate melting at 75° C.

Workup

  1. customThe tube is evacuated
  2. additionfilled with argon
  3. customsealed
  4. additionthe mixture is diluted with ethyl acetate and water
  5. extractionthe aqueous phase is extracted with ethyl acetate
  6. dry with materialThe pooled organic extracts are dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5)

Sources & evidence

ORD record
ord-1ea9ce72e2c34269a08dc778da1aceda
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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