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

HRID 423678Notes

Reaction equation

HRID 423678 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 24994965(r)-2-[2-Fluoro-4-(methylsulfinyl)phenyl]-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridineYield 16.4%

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 (32 mg) was isolated as an off-white solid with Tr of 11.25 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-c57685b5e1394b3f85b53df71227ea93
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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