Sodium Bicarbonate → (+)-1-{[6-Chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)pyrrolidin-2-one

HRID 69562Notes

Reaction equation

HRID 69562 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[Cl:5][C:6]1[N:7]=[C:8]2[N:12]([CH:13]=1)[N:11]=[C:10]([CH2:14][O:15][CH3:16])[S:9]2.Cl[CH2:18][N:19]1[CH2:23][CH:22]([CH2:24][CH2:25][C:26]([F:29])([F:28])[F:27])[CH2:21][C:20]1=[O:30].C([O-])(O)=O.[Na+]>O1CCOCC1>[Cl:5][C:6]1[N:7]=[C:8]2[N:12]([C:13]=1[CH2:18][N:19]1[CH2:23][CH:22]([CH2:24][CH2:25][C:26]([F:29])([F:28])[F:27])[CH2:21][C:20]1=[O:30])[N:11]=[C:10]([CH2:14][O:15][CH3:16])[S:9]2

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 6451240Aluminum(III) ChlorideHCID 671165026-Chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazoleHCID 67116751HCID 67116751, compound

Product 1

HCID 52911733(+)-1-{[6-Chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)pyrrolidin-2-oneYield 56%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
85 °C

Procedure

To a hot solution (80° C.) of AlCl3 (0.842 g, 6.3 mmol, 1 eq) and 6-chloro-2-(methoxy-methyl)imidazo[2,1-b][1,3,4]thiadiazole a35 (0.643 g, 3.156 mmol, 1 eq) in dioxane (35 ml) is added a solution of 1-(chloromethyl)-4-(3,3,3-trifluoropropyl)pyrrolidin-2-one a20 (1.2 g) in dioxane (5 ml). The reaction mixture is heated at 85° C. for 3 days. After cooling and hydrolysis by a saturated solution of NaHCO3 (40 ml), the crude reaction mixture is extracted by ethyl acetate (3×25 ml). The cumulated organic layers are dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified by chromatography over silicagel (eluent CH2Cl2/MeOH/NH4OH 99:1:0.1) and recrystallized from diisopropyl ether to afford pure (+)-1-{[6-chloro-2-(methoxymethyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)pyrrolidin-2-one 27.

Workup

  1. temperatureAfter cooling
  2. customthe crude reaction mixture
  3. extractionis extracted by ethyl acetate (3×25 ml)
  4. dry with materialThe cumulated organic layers are dried over MgSO4
  5. filtrationfiltered
  6. customcondensed under reduced pressure
  7. customThe residue is purified by chromatography over silicagel (eluent CH2Cl2/MeOH/NH4OH 99:1:0.1)
  8. customrecrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-35efeab18aea481db28407ccebeba000
Source dataset
uspto-grants-2014_09
Patent number
US08822508B2

Reaction notes

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