HCID 71197908, compound → Methyl [2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}Piperidin-4-yl)-5-Chlorophenyl]acetate

HRID 2415543Notes

Reaction equation

HRID 2415543 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[CH2:33][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](=O)=O>[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[CH2:33][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 71197908HCID 71197908, compound

Product 1

HCID 86590372Methyl [2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}Piperidin-4-yl)-5-Chlorophenyl]acetateYield 90.2%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 702EthanolSolvent

Procedure

A mixture of methyl [2-(1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-1,2,3,6-tetrahydropyridin-4-yl)-5-chlorophenyl]acetate (1-8) (2.60 mmol) and platinum (IV) oxide (0.300 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®, eluting 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 1-9 (1.25 g) as a colorless foam (m/z (ES) 533 (MH+).

Workup

  1. filtrationThe resulting mixture was filtered through a short column of celite®
  2. washeluting 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-515c5e94e8ed4fd5847e9f8f14274545
Source dataset
uspto-grants-2004_11
Patent number
US06818658B2

Reaction notes

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