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Lithium Hydroxide → (S)-4-(4-((4'-Chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid

HRID 1476304
ノート
印刷プレビュー

反応式

HRID 1476304 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@@H:14]([OH:32])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27]CC)=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1.[Li+].[OH-]>C1COCC1.CO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@@H:14]([OH:32])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:30][CH:31]=3)[CH2:17][CH2:16]2)=[CH:6][CH:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 2

HCID 3939Lithium HydroxideHCID 56650672(S)-Ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate2 回

生成物 1

HCID 58080142(S)-4-(4-((4'-Chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒
HCID 8028
Tetrahydrofuran
溶媒

実験手順

(S)-Ethyl 4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate (INTERMEDIATE 11B, 150.0 mg, 0.33 mmol) was dissolved in THF (6.0 ml) and methanol (1.4 ml). A solution of LiOH (40.6 mg) in water (1.4 ml) was added. The solution was heated at 50° overnight. The reaction mixture was allowed to cool to room temperature and then concentrated under reduced pressure. The residue was diluted with water (5 ml), acidified with 1N aq. HCl (2.0 ml), and extracted with DCM (2×5 ml). The extract was dried (MgSO4), filtered through cotton, and evaporated under vacuum to provide the title product as a substantially separated enantiomer (155 mg, yield: almost quantitative) 1H NMR (400 MHz, DICHLOROMETHANE-d2) δ ppm 0.79-0.94 (m, 1 H) 0.98-1.12 (m, 1 H) 1.14-1.40 (m, 4 H) 2.04 (m, 1 H) 2.67 (td, J=12.51, 2.78 Hz, 1 H) 2.78 (td, 1 H) 3.74 (d, 1 H) 3.91 (m, 1 H) 4.48 (d, 1 H) 6.81 (d, 2 H) 7.17-7.29 (m, 3 H) 7.31-7.49 (m, 4 H) 7.61 (dd, 1 H) 7.84-7.93 (m, 2 H).

後処理

  1. temperatureThe solution was heated at 50° overnight
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with water (5 ml)
  4. extractionextracted with DCM (2×5 ml)
  5. dry with materialThe extract was dried (MgSO4)
  6. filtrationfiltered through cotton
  7. customevaporated under vacuum

出典と根拠

ORDレコード
ord-36c83ba63fa24301bc38db7c6ea12af3
出典データセット
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09018381B2

反応ノート

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