Methanol → 2-methyl-1-[4-[[6-(1-methylsulfonyl-3,6-dihydro-2H-pyridin-4-yl)-3-pyridyl]oxymethyl]-1-piperidyl]propan-2-ol

HRID 222585

Reaction equation

HRID 222585 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH:9]=[C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[CH:13][N:12]=2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].C[CH:26]1[O:28][CH:27]1[CH3:29].[CH3:30]O>>[CH3:1][S:2]([N:5]1[CH2:6][CH:7]=[C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]3[CH2:24][CH2:23][N:22]([CH2:26][C:27]([CH3:29])([OH:28])[CH3:30])[CH2:21][CH2:20]3)=[CH:13][N:12]=2)[CH2:9][CH2:10]1)(=[O:3])=[O:4]

Participants

4

Reactant 3

HCID 887Methanol2×HCID 186322-Butylene oxideHCID 66864837HCID 66864837, compound

Product 1

HCID 668647472-methyl-1-[4-[[6-(1-methylsulfonyl-3,6-dihydro-2H-pyridin-4-yl)-3-pyridyl]oxymethyl]-1-piperidyl]propan-2-ol

Procedure

4-(1′-Methanesulfonyl-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-5-yloxymethyl)-piperidine is suspended in 800 mL of methanol and added to an autoclave with a mechanical stirrer. 1500 mL of methanol are added and then dimethyloxirane (117 g, 1.62 mol) is added. The mixture is stirred at 60˜70° C. for 88 h, cooled to 25˜30° C. and concentrated to 1000 mL. The mixture is heated at 60˜70° C. and 4200 mL of water are added. The resulting mixture is stirred at 60˜70° C. during 30 min and cooled slowly to 0˜5° C. in 1.5˜2 h. It is stirred at this temperature for 30 minutes and filtered. The cake is slurried with H2O: MeOH=3:1 (600 mL) pre-cooled to 0˜5° C. and concentrated (2×). The product is dried under vacuum at 40˜50° C. to provide 320 g of off-white solid with 98.3% HPLC purity.

Workup

  1. additionadded to an autoclave with a mechanical stirrer
  2. temperaturecooled to 25˜30° C.
  3. concentrationconcentrated to 1000 mL
  4. temperatureThe mixture is heated at 60˜70° C.
  5. addition4200 mL of water are added
  6. stirringThe resulting mixture is stirred at 60˜70° C. during 30 min
  7. temperaturecooled slowly to 0˜5° C. in 1.5˜2 h
  8. stirringIt is stirred at this temperature for 30 minutes
  9. filtrationfiltered
  10. temperatureMeOH=3:1 (600 mL) pre-cooled to 0˜5° C.
  11. concentrationconcentrated (2×)
  12. customThe product is dried under vacuum at 40˜50° C.

Sources & evidence

ORD record
ord-ff3ed466ecfd4a24845038160a411a61
Source dataset
uspto-grants-2012_06
Patent number
US08207344B2

Linked notes

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