(4-Fluoro-phenyl)-(5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-methanone → ((S)-5-pyrrolidin-2-yl-pyridin-3-yl)-methanone

HRID 1038650Notes

Reaction equation

HRID 1038650 reaction equation
FC1C=CC([C:8]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([C@@H:16]3[CH2:20][CH2:19][CH2:18][N:17]3[C@@H](C3C=CC(OC)=CC=3)C)[CH:15]=2)=[O:9])=CC=1>C(O)(C(F)(F)F)=O>[NH:17]1[CH2:18][CH2:19][CH2:20][C@H:16]1[C:14]1[CH:15]=[C:10]([CH:8]=[O:9])[CH:11]=[N:12][CH:13]=1

Participants

3

Reactant 1

HCID 69810699(4-Fluoro-phenyl)-(5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-methanone

Product 1

HCID 86652067((S)-5-pyrrolidin-2-yl-pyridin-3-yl)-methanoneYield 109.1%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (4-fluoro-phenyl)-(5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-methanone (4) (3.3 g, 8.17 mmole) in 5 mL of TFA is heated at 100° C. in a microwave reactor for 30 minutes. The result solution is concentrated to remove TFA. The residue is diluted with 100 mL of CH2Cl2, and basified by washing with 5 mL of saturated sodium bicarbonate. The organic layer is concentrated and purified by flash column chromatography (CH2Cl2 100% to CH2Cl2 80% MeOH 20% gradient in 30 minutes) to give 4-fluoro-phenyl)-((S)-5-pyrrolidin-2-yl-pyridin-3-yl)-methanone (5) (1.57 g, yield 71%) as a light brown viscose liquid.

Workup

  1. concentrationThe result solution is concentrated
  2. customto remove TFA
  3. additionThe residue is diluted with 100 mL of CH2Cl2
  4. washby washing with 5 mL of saturated sodium bicarbonate
  5. concentrationThe organic layer is concentrated
  6. custompurified by flash column chromatography (CH2Cl2 100% to CH2Cl2 80% MeOH 20% gradient in 30 minutes)

Sources & evidence

ORD record
ord-1fb453171c184f2282d7eb14b2e3955f
Source dataset
uspto-grants-2013_10
Patent number
US08552003B2

Reaction notes

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