Diisopropylethylamine → (S)-methyl 5-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)picolinate

HRID 407992Notes

Reaction equation

HRID 407992 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([F:9])[C:5](F)=[N:6][CH:7]=1.Cl.[O:11]=[C:12]1[C@@H:16]([O:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]([O:26][CH3:27])=[O:25])=[N:22][CH:23]=2)[CH2:15][CH2:14][N:13]1[CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([F:9])[C:5]([N:31]2[CH2:32][CH2:33][CH:28]([N:13]3[CH2:14][CH2:15][C@H:16]([O:17][C:18]4[CH:19]=[CH:20][C:21]([C:24]([O:26][CH3:27])=[O:25])=[N:22][CH:23]=4)[C:12]3=[O:11])[CH2:29][CH2:30]2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27832485-Chloro-2,3-difluoropyridineHCID 67469702(S)-methyl 5-(2-oxo-1-(piperidin-4-yl)pyrrolidin-3-yloxy)picolinate hydrochloride

Product 1

HCID 67469713(S)-methyl 5-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)picolinateYield 86.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

5-Chloro-2,3-difluoropyridine (0.20 g, 1.3 mmol) was added to a mixture of (S)-methyl 5-(2-oxo-1-(piperidin-4-yl)pyrrolidin-3-yloxy)picolinate hydrochloride (0.17 g, 0.44 mmol) and DIEA (0.38 mL, 2.2 mmol) in DMF (1.5 mL). The mixture was stirred at 100° C. overnight and then cooled to ambient temperature. The mixture was partitioned between saturated aqueous NH4Cl (20 mL) and EtOAc (50 mL). The organic phase was washed successively with water (20 mL), water (20 mL) and then brine (20 mL). The combined organic phases were dried over MgSO4, filtered and concentrated. The residue was purified on silica (eluting with EtOAc) to afford (S)-methyl 5-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)picolinate (0.17 g, 0.38 mmol, 86%).

Workup

  1. temperaturecooled to ambient temperature
  2. customThe mixture was partitioned between saturated aqueous NH4Cl (20 mL) and EtOAc (50 mL)
  3. washThe organic phase was washed successively with water (20 mL), water (20 mL)
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica (eluting with EtOAc)

Sources & evidence

ORD record
ord-4add5062469b45f485d791a4f8906f23
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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