Diisopropylethylamine → 2-(4-Fluorophenyl)-2-[3-[4-(6-fluorobenzo[b]thiophen-3-yl)piperidin-1-yl]propyl]-1,3-dioxolane

HRID 2186797Notes

Reaction equation

HRID 2186797 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:13][CH2:14][CH2:15]Cl)[O:12][CH2:11][CH2:10][O:9]2)=[CH:4][CH:3]=1.Cl.[F:18][C:19]1[CH:20]=[CH:21][C:22]2[C:26]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[CH:25][S:24][C:23]=2[CH:33]=1.C(N(C(C)C)CC)(C)C>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:13][CH2:14][CH2:15][N:30]3[CH2:31][CH2:32][CH:27]([C:26]4[C:22]5[CH:21]=[CH:20][C:19]([F:18])=[CH:33][C:23]=5[S:24][CH:25]=4)[CH2:28][CH2:29]3)[O:12][CH2:11][CH2:10][O:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27237782-(3-Chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolaneHCID 226493344-(6-Fluorobenzo(b)thiophen-3-yl)piperidine hydrochloride

Product 1

HCID 226493442-(4-Fluorophenyl)-2-[3-[4-(6-fluorobenzo[b]thiophen-3-yl)piperidin-1-yl]propyl]-1,3-dioxolaneYield 29%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 1.5 g of 2-(4-fluorophenyl)-2-(3-chloropropyl)-1,3-dioxolane, 1.5 g of 4-(6-fluorobenzo[b]thiophen-3-yl)piperidine hydrochloride, 3.3 ml of diisopropylethylamine and 2.5 ml of methanol was stirred with heating under reflux for 25 hours. The reaction mixture was separated with chloroform and a saturated aqueous sodium hydrogencarbonate solution, and the aqueous layer was extracted with chloroform. The combined organic layer was washed with water and a saturated aqueous sodium chloride solution and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by a flush chromatography (silica gel: Merckkieselgel 60 230-to 400-mesh, eluent: hexane-ethyl acetate=1:2) to obtain 0.71 g of 2-(4-fluorophenyl)-2-[3-[4-(6-fluorobenzo[b]thiophen-3-yl)piperidin-1-yl]propyl]-1,3-dioxolane.

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 25 hours
  3. customThe reaction mixture was separated with chloroform
  4. extractiona saturated aqueous sodium hydrogencarbonate solution, and the aqueous layer was extracted with chloroform
  5. washThe combined organic layer was washed with water
  6. dry with materiala saturated aqueous sodium chloride solution and then dried over magnesium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe residue was purified by a flush chromatography (silica gel: Merckkieselgel 60 230-to 400-mesh, eluent: hexane-ethyl acetate=1:2)

Sources & evidence

ORD record
ord-953fede6eab24019ae4cc947a170f570
Source dataset
uspto-grants-2002_06
Patent number
US06407121B1

Reaction notes

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