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

HRID 1771201
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HRID 1771201 반응식
[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
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참가 물질

6

반응물 2

HCID 3939Lithium HydroxideHCID 56650672(S)-Ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate2회

생성물 1

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

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매
HCID 8028
Tetrahydrofuran
용매

실험 절차

(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 500 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, 1H) 0.98-1.12 (m, 1H) 1.14-1.40 (m, 4H) 2.04 (m, 1H) 2.67 (td, J=12.51, 2.78 Hz, 1H) 2.78 (td, 1H) 3.74 (d, 1H) 3.91 (m, 1H) 4.48 (d, 1H) 6.81 (d, 2H) 7.17-7.29 (m, 3H) 7.31-7.49 (m, 4H) 7.61 (dd, 1H) 7.84-7.93 (m, 2H).

후처리

  1. temperatureThe solution was heated at 500 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

출처 및 근거

ORD 기록
ord-13a72434d4ac44f38f4a79a7ed1e058e
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09248140B2

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