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

HRID 423679Notes

Reaction equation

HRID 423679 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25]3[O:29][N:28]=[C:27]([CH:30]([CH3:32])[CH3:31])[N:26]=3)[CH2:21][CH2:20]2)=[CH:13][N:12]=1.C(=O)=O.CO>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([S@:8]([CH3:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25]3[O:29][N:28]=[C:27]([CH:30]([CH3:32])[CH3:31])[N:26]=3)[CH2:21][CH2:20]2)=[CH:13][N:12]=1

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 887MethanolHCID 59177837HCID 59177837, compound

Product 1

HCID 59177836(s)-2-[2-Fluoro-4-(methylsulfinyl)phenyl]-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridineYield 20%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

The racemic sulfoxide 2-[2-fluoro-4-(methylsulfinyl)phenyl]-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridine (prepared as in Example 176, 195 mg) was subjected to Chiral HPLC [column: Chiralpak AS-H, column mobile phase: 65% CO2: 35% (80% MeOH: 20% CHCl3) (2 mL/min), pressure 140 bar, temperature 30° C., 280 nm] analysis and then separation to give two (R and S) enantiomers. The title compound (39 mg) was isolated as an off-white solid with Tr of 16.69 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-69d6ac93e06943ac8c659676402a6748
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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