Carbon Dioxide → (s)-5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfinyl)phenyl]pyridine

HRID 423681Notes

Reaction equation

HRID 423681 reaction equation
[CH3:1][CH:2]([C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][O:16][C:17]3[CH:18]=[CH:19][C:20]([C:23]4[CH:28]=[CH:27][C:26]([S:29]([CH3:31])=[O:30])=[CH:25][CH:24]=4)=[N:21][CH:22]=3)[CH2:11][CH2:10]2)[O:6][N:5]=1)[CH3:3].C(=O)=O.CO>C(Cl)(Cl)Cl>[CH3:3][CH:2]([C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][O:16][C:17]3[CH:18]=[CH:19][C:20]([C:23]4[CH:28]=[CH:27][C:26]([S@:29]([CH3:31])=[O:30])=[CH:25][CH:24]=4)=[N:21][CH:22]=3)[CH2:11][CH2:10]2)[O:6][N:5]=1)[CH3:1]

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 887MethanolHCID 46861617(+/-)-5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfinyl)phenyl]pyridine

Product 1

HCID 59177783(s)-5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfinyl)phenyl]pyridineYield 9.7%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

The racemic sulfoxide 5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfinyl)phenyl]pyridine (prepared as in Example 171, 290 mg) was subjected to Chiral HPLC [column: Chiralcel OJ-H, column mobile phase: 80% CO2: 20% (80% MeOH: 20% CHCl3) (2 mL/min), pressure 140 bar, temperature 30° C., 254 nm] analysis and then separation to give two (R and S) enantiomers. The title compound (28 mg) was isolated a tan solid with Tr of 12.11 min (second eluting peak). The (S) absolute stereochemistry was assigned by Ab initio VCD analysis.

Workup

  1. customseparation
  2. customto give two (R and S) enantiomers

Sources & evidence

ORD record
ord-b5b0e21254b24166b03f42d9ddbf5791
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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