Pyrrolidine → (S)-1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(pyrrolidine-1-carbonyl)phenoxy)pyrrolidin-2-one

HRID 408003Notes

Reaction equation

HRID 408003 reaction equation
[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:22][CH2:21][C@H:20]([O:23][C:24]4[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][C:25]=4[F:33])[C:19]3=[O:34])[CH2:14][CH2:13]2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[NH:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[C:3]([N:12]2[CH2:13][CH2:14][CH:15]([N:18]3[CH2:22][CH2:21][C@H:20]([O:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([N:35]5[CH2:39][CH2:38][CH2:37][CH2:36]5)=[O:29])=[CH:26][C:25]=4[F:33])[C:19]3=[O:34])[CH2:16][CH2:17]2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1

Participants

5

Reactant 2

HCID 31268PyrrolidineHCID 67469817(S)-4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid

Product 1

HCID 54670803(S)-1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(pyrrolidine-1-carbonyl)phenoxy)pyrrolidin-2-oneYield 6.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-4-(1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid (0.040 g, 0.080 mmol) and pyrrolidine (0.028 g, 0.40 mmol) in DMF (1 mL) was added HTBU (0.060 g, 0.16 mmol) and the reaction was stirred overnight at ambient temperature. The reaction was diluted with EtOAc (20 mL) and washed with 1 N HCl (5 mL), 1 N NaOH (5 mL), and brine (5 mL), and the combined organic phases were dried over MgSO4, and concentrated under vacuum. The material was purified on silica, using EtOAc as eluent to yield (S)-1-(1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(pyrrolidine-1-carbonyl)phenoxy)pyrrolidin-2-one (0.0026 g, 0.005 mmol, 6% yield). Mass spectrum (apci) m/z=555.0 (M+H).

Workup

  1. washwashed with 1 N HCl (5 mL), 1 N NaOH (5 mL), and brine (5 mL)
  2. dry with materialthe combined organic phases were dried over MgSO4
  3. concentrationconcentrated under vacuum
  4. customThe material was purified on silica

Sources & evidence

ORD record
ord-efb229304e754c71b2a1fc464cf0559c
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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