Hydrochloric Acid → [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetic acid

HRID 1187380Notes

Reaction equation

HRID 1187380 reaction equation
[OH-].[Na+].[CH3:3][N:4]([CH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)[C:5]([C:7]1[CH:8]=[CH:9][C:10]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([CH2:23][C:24]([O:26]C)=[O:25])[CH2:18]2)=[N:11][C:12]=1[S:13][CH2:14][CH2:15][CH3:16])=[O:6].Cl>O.CO.CCOC(C)=O.C(Cl)Cl>[CH3:3][N:4]([CH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)[C:5]([C:7]1[CH:8]=[CH:9][C:10]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([CH2:23][C:24]([OH:26])=[O:25])[CH2:18]2)=[N:11][C:12]=1[S:13][CH2:14][CH2:15][CH3:16])=[O:6]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59830659methyl [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetate

Product 1

HCID 59830715[(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetic acidYield 100%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
18 °C

Procedure

A solution of sodium hydroxide (0.130 g, 3.25 mmol) in water (1.63 mL) was added dropwise to a stirred solution of methyl [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetate (293 mg, 0.65 mmol) in MeOH (5 mL) at 18° C., over a period of 1 minute. The resulting solution was stirred at 18° C. for 20 hours. The reaction mixture was adjusted to pH 4.5 with 2M HCl and the reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with water (20 mL) and saturated brine (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The residue was dissolved in DCM (10 ml) and the slight suspension filtered through a nylon millipore filter to remove the solid. Evaporation gave the product, [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetic acid (281 mg, 100%), as a white solid

Workup

  1. washwashed sequentially with water (20 mL) and saturated brine (20 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. filtrationthe slight suspension filtered through a nylon
  7. filtrationmillipore filter
  8. customto remove the solid
  9. customEvaporation

Sources & evidence

ORD record
ord-f15b3de780904459afe9f78808cdcbf4
Source dataset
uspto-grants-2014_03
Patent number
US08673938B2

Reaction notes

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