Chloroform → racemic 1-[4-(2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridin-8-yl)piperidin-1-yl]ethanone

HRID 546712Notes

Reaction equation

HRID 546712 reaction equation
[OH-].[Na+].[C:3](Cl)(=[O:5])[CH3:4].[CH3:7][O:8][C:9]1[CH:10]=[C:11](/[CH:21]=[CH:22]/[C:23]2[N:37]=[C:26]3[CH:27]([CH:31]4[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]4)[CH2:28][CH2:29][CH2:30][N:25]3[N:24]=2)[CH:12]=[CH:13][C:14]=1[N:15]1[CH:19]=[C:18]([CH3:20])[N:17]=[CH:16]1.C(Cl)(Cl)Cl>C(Cl)Cl>[CH3:7][O:8][C:9]1[CH:10]=[C:11](/[CH:21]=[CH:22]/[C:23]2[N:37]=[C:26]3[CH:27]([CH:31]4[CH2:32][CH2:33][N:34]([C:3](=[O:5])[CH3:4])[CH2:35][CH2:36]4)[CH2:28][CH2:29][CH2:30][N:25]3[N:24]=2)[CH:12]=[CH:13][C:14]=1[N:15]1[CH:19]=[C:18]([CH3:20])[N:17]=[CH:16]1

Participants

6

Reactant 4

HCID 6212ChloroformHCID 6367Acetyl chlorideHCID 14798Sodium HydroxideHCID 668394842-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(piperidin-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine

Product 1

HCID 66839366racemic 1-[4-(2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridin-8-yl)piperidin-1-yl]ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 1 N sodium hydroxide solution (0.5 ml) and acetyl chloride (14 ul) were added to a solution of racemic 2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(piperidin-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine obtained in Examples 118 and 119 (25 mg) in methylene chloride (0.5 ml), and the reaction solution was stirred at room temperature for 40 minutes. Chloroform was added to the reaction solution, and the organic layer was separated. The aqueous layer was reextracted with chloroform twice. The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 25 mg of racemic 1-[4-(2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridin-8-yl)piperidin-1-yl]ethanone. Then, the racemate was separated by CHIRALPAK™ IA manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: ethanol) to obtain the title optically active compound with a retention time of 27 minutes and positive optical rotation (7.4 mg; 100% ee) and the title optically active compound with a retention time of 34 minutes and negative optical rotation (6.7 mg; 97% ee)

Workup

  1. customthe organic layer was separated
  2. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f97b8270edcb4502bf9315643cc19ce7
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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