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 2415549ノート

反応式

HRID 2415549 の反応式
[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]

参加物

4

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 23939Platinum触媒HCID 702Ethanol溶媒

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-213964a08e3a4acd8eaa46cb783a952f
出典データセット
uspto-grants-2004_11
特許番号
US06818658B2

反応ノート

読み込み中…