Methyl 2-[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}-1,2,3,6-Tetrahydropyridin-4-yl)-5-Chlorophenyl]Propanoate → Methyl 2-[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}Piperidin-4-yl)-5-Chlorophenyl]Propanoate

HRID 2415549Notes

Reaction equation

HRID 2415549 reaction equation
[C:1]([N:5]1[CH2:9][C@@H:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[C@H:7]([C:18]([N:20]2[CH2:25][CH:24]=[C:23]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[CH:33]([CH3:38])[C:34]([O:36][CH3:37])=[O:35])[CH2:22][CH2:21]2)=[O:19])[CH2:6]1)([CH3:4])([CH3:3])[CH3:2]>C(O)C.[Pt]>[C:1]([N:5]1[CH2:9][C@@H:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[C@H:7]([C:18]([N:20]2[CH2:25][CH2:24][CH:23]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[CH:33]([CH3:38])[C:34]([O:36][CH3:37])=[O:35])[CH2:22][CH2:21]2)=[O:19])[CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 1

HCID 69362634Methyl 2-[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}-1,2,3,6-Tetrahydropyridin-4-yl)-5-Chlorophenyl]Propanoate

Product 1

HCID 69363870Methyl 2-[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}Piperidin-4-yl)-5-Chlorophenyl]PropanoateYield 90.4%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 702EthanolSolvent

Procedure

A mixture of methyl 2-[2-(1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-1,2,3,6-tetrahydropyridin-4-yl)-5-chlorophenyl]propanoate (2-4) (1.92 mmol) and platinum (TV) oxide (0.350 g) in ethanol/glacial acetic acid (1:1, 20 mL) was hydrogenated at atmospheric pressure for approximately 15 h. The resulting mixture was filtered through a short column of celite®, eluted copiously with ethanol. The filtrate was evaporated and the residue was partitioned between methylene chloride and saturated aqueous sodium bicarbonate. The organic layer was separated and the aqueous phase was re-extracted twice with methylene chloride. The combined organic extracts were washed with water, brine, dried (Na2SO4), and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 0-15% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent) furnished 2-5 (0.95 g) as a colorless foam (m/z (ES) 547 (MH+).

Workup

  1. filtrationThe resulting mixture was filtered through a short column of celite®
  2. washeluted copiously with ethanol
  3. customThe filtrate was evaporated
  4. customthe residue was partitioned between methylene chloride and saturated aqueous sodium bicarbonate
  5. customThe organic layer was separated
  6. extractionthe aqueous phase was re-extracted twice with methylene chloride
  7. washThe combined organic extracts were washed with water, brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 0-15% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent)

Sources & evidence

ORD record
ord-213964a08e3a4acd8eaa46cb783a952f
Source dataset
uspto-grants-2004_11
Patent number
US06818658B2

Reaction notes

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