Acetic Acid → (R)-1-{5-[(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamino]-2-methyl-benzyl}-pyrrolidine-3-carboxylic acid

HRID 1629726ノート

反応式

HRID 1629726 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([CH3:22])=[C:18]([CH:21]=2)[CH:19]=O)[C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[CH3:23].[NH:24]1[CH2:28][CH2:27][C@@H:26]([C:29]([OH:31])=[O:30])[CH2:25]1.CC(O)=O>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([CH3:22])=[C:18]([CH:21]=2)[CH2:19][N:24]2[CH2:28][CH2:27][C@@H:26]([C:29]([OH:31])=[O:30])[CH2:25]2)[C:9]([F:11])([F:12])[F:10])=[CH:4][C:3]=1[CH3:23]

参加物

5

反応物 3

HCID 176Acetic AcidHCID 1501970(3R)-3-Pyrrolidinecarboxylic acidHCID 866562265-[(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamino]-2-methyl-benzaldehyde

生成物 1

HCID 53340673(R)-1-{5-[(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamino]-2-methyl-benzyl}-pyrrolidine-3-carboxylic acid

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a solution of aldehyde INT 33 (2.50 g, 7.32 mmol) and (R)-pyrrolidine-3-carboxylic acid (0.93 g, 8.05 mmol) in MeOH (74 mL) was added HOAc (0.42 mL, 7.32 mmol) followed by PS—CNBH3 (2.5 mmol/g, 2.93 g, 7.32 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was filtered through Celite. The filtrate was concentrated. The residue was taken up in EtOAc and washed with saturated aqueous NaHCO3 and water. The aqueous layers were extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel (CH2Cl2/MeOH) to afford the title compound Example 21.

後処理

  1. filtrationThe mixture was filtered through Celite
  2. concentrationThe filtrate was concentrated
  3. washwashed with saturated aqueous NaHCO3 and water
  4. extractionThe aqueous layers were extracted with EtOAc (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (CH2Cl2/MeOH)

出典と根拠

ORDレコード
ord-85fc6a5fcf504090b9a28880a614e43d
出典データセット
uspto-grants-2014_07
特許番号
US08791100B2

反応ノート

読み込み中…