Methanol → HCID 86707210, compound

HRID 1854232Notes

Reaction equation

HRID 1854232 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([O-:5])=[O:4].[CH3:8][CH:9]([NH+:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C@@H:19]1[C:24]([NH:26][C@H:27]([C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35]C)=[O:34])=[CH:31][CH:30]=1)[CH3:28])=[O:25])[CH2:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CO.[OH-].[Na+]>C1COCC1>[F:1][C:2]([F:7])([F:6])[C:3]([O-:5])=[O:4].[CH3:8][CH:9]([NH+:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C@@H:19]1[C:24]([NH:26][C@H:27]([C:29]1[CH:30]=[CH:31][C:32]([C:33]([OH:35])=[O:34])=[CH:37][CH:38]=1)[CH3:28])=[O:25])[CH2:10][O:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 86707212HCID 86707212, compound

Product 1

HCID 86707210HCID 86707210, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Dissolve methyl 4-[(1S)-1-[[(2R)-1-(1-methyl-2-phenoxyethyl)piperidinium-2-carbonyl]amino]ethyl]benzoate trifluoroacetate (24 mg, 0.045 mmol) in THF (226 μL) and treat the mixture with methanol (226 μL) and sodium hydroxide (1 N aqueous solution, 170 μL, 0.17 mmol). Stir the mixture overnight at room temperature, then concentrate under reduced pressure to furnish a gummy solid. Subject the crude material to reverse-phase chromatography on C18 silica gel, eluting with 0.1% TFA in a gradient of 5% to 50% ACN/water to furnish two separate fractions, each containing a separate diastereomer of product. Concentrate each fraction under reduced pressure, dissolve each in a minimal volume of methanol, triturate each with diethyl ether (5 mL), and concentrate each under reduced pressure to furnish Isomer 1 (3.0 mg, 13% yield) and Isomer 2 (1.1 mg, 5% yield) of the title compound as white solids.

Workup

  1. concentrationconcentrate under reduced pressure
  2. customto furnish a gummy solid
  3. washeluting with 0.1% TFA in a gradient of 5% to 50% ACN/water
  4. customto furnish two
  5. customseparate fractions
  6. concentrationConcentrate each fraction under reduced pressure
  7. dissolutiondissolve each in a minimal volume of methanol
  8. customtriturate each with diethyl ether (5 mL)
  9. concentrationconcentrate each under reduced pressure

Sources & evidence

ORD record
ord-b85a48654fdf47b4a1ccdacc010e82c4
Source dataset
uspto-grants-2015_02
Patent number
US08962659B2

Reaction notes

Loading…