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

HRID 423680Notes

Reaction equation

HRID 423680 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 24994966(r)-5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfinyl)phenyl]pyridineYield 8.6%

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 (25 mg) was isolated a tan solid with Tr of 11.15 min (first eluting peak). The (R) 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-b3cd6e6ec5bb4d1fa286c387a06353c8
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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