Diisopropylethylamine → (S)-methyl 4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoate

HRID 408001Notes

Reaction equation

HRID 408001 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[O:13][C@H:14]1[CH2:18][CH2:17][N:16]([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[C:15]1=[O:25])[C:6]([O:8][CH3:9])=[O:7].C(N(C(C)C)C(C)C)C.Cl[C:36]1[C:41]([Cl:42])=[CH:40][C:39]([C:43]([F:46])([F:45])[F:44])=[CH:38][N:37]=1>CN(C=O)C.CCOC(C)=O>[Cl:42][C:41]1[C:36]([N:22]2[CH2:23][CH2:24][CH:19]([N:16]3[CH2:17][CH2:18][C@H:14]([O:13][C:12]4[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=4[F:2])[C:15]3=[O:25])[CH2:20][CH2:21]2)=[N:37][CH:38]=[C:39]([C:43]([F:45])([F:44])[F:46])[CH:40]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1122342,3-Dichloro-5-(trifluoromethyl)pyridineHCID 67469793(S)-methyl 3-fluoro-4-(2-oxo-1-(piperidin-4-yl)pyrrolidin-3-yloxy)benzoate hydrochloride

Product 1

HCID 54670990(S)-methyl 4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoateYield 66.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-methyl 3-fluoro-4-(2-oxo-1-(piperidin-4-yl)pyrrolidin-3-yloxy)benzoate hydrochloride (0.1 g, 0.29 mmol) in DMF (10 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.543 mL, 2.97 mmol) and 2,3-dichloro-5-(trifluoromethyl)pyridine (0.193 g, 0.892 mmol) and the reaction was stirred overnight at ambient temperature. The reaction was diluted with EtOAc (50 mL) and washed with water (20 mL), and brine (20 mL), dried over MgSO4, filtered and concentrated under vacuum. The material was purified on silica, using a gradient of DCM to 10% EtOAc/DCM as eluent to yield (S)-methyl 4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoate (0.10 g, 63% yield).

Workup

  1. washwashed with water (20 mL), and brine (20 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe material was purified on silica

Sources & evidence

ORD record
ord-0a30a5d4068f4112bcfe31b91efb3736
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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