Lithium Hydroxide → (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-hydroxypyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

HRID 132964ノート

反応式

HRID 132964 の反応式
[C:1]([NH:4][C@:5]1([C@@H:54]([CH2:56][CH3:57])[CH3:55])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:45][CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:11]([NH:13][C@@H:14]([CH2:36][C:37]2[CH:42]=[C:41]([F:43])[CH:40]=[C:39]([F:44])[CH:38]=2)[C@@H:15]([C@H:17]2[CH2:22][CH2:21][CH2:20]C[N:18]2C(C2C=CC=CC=2)C2C=CC=CC=2)[OH:16])=[O:12])[C:6]1=[O:53])(=[O:3])[CH3:2].N[C@@H](CC1C=C(F)C=C(F)C=1)[C@@H]([C@@H]1N(C(C2C=CC=CC=2)C2C=CC=CC=2)C[C@H](O)C1)[OH:61].FC1C=C(C=C(F)C=1)C[C@H]1[C@@H]([C@H]2C[C@@H](O)CN2C(C2C=CC=CC=2)C2C=CC=CC=2)OC(=O)N1.[Li+].[OH-]>CCO.O>[C:1]([NH:4][C@:5]1([C@@H:54]([CH2:56][CH3:57])[CH3:55])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:45][CH2:46][C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:11]([NH:13][C@@H:14]([CH2:36][C:37]2[CH:38]=[C:39]([F:44])[CH:40]=[C:41]([F:43])[CH:42]=2)[C@H:15]([OH:16])[C@H:17]2[CH2:22][C@@H:21]([OH:61])[CH2:20][NH:18]2)=[O:12])[C:6]1=[O:53])(=[O:3])[CH3:2]

参加物

7

反応物 4

HCID 3939Lithium HydroxideHCID 58608196(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-oneHCID 69194179(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamideHCID 69195568(3R,5R)-5-((1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl)-1-benzhydrylpyrrolidin-3-ol

生成物 1

HCID 69196515(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-hydroxypyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

実験手順

Step 14 (A): (3R,5R)-5-((1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl)-1-benzhydrylpyrrolidin-3-ol. To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation J, 129 mg, 0.278 mmol) in EtOH (10 mL) was added a solution of LiOH (133 mg, 5.56 mmol) in H2O (2.5 mL). This reaction mixture was stirred at reflux for 3.5 h. After cooling down to rt, the mixture was concentrated to remove EtOH and the mixture was extracted with ethyl acetate and the organic phase was washed with sat. aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Flash chromatography (silica gel, 0-10% MeOH/chloroform) gave the title compound: 1H NMR (CDCl3, 500 MHz) δ 2.00-2.05 (1H, m), 2.13-2.21 (1H, m), 2.40-2.61 (2H, m), 2.79-2.91 (2H, m), 3.21 (2H, d, J=15 Hz), 3.51 (1H, d, J=15 Hz), 4.26 (1H, m), 4.79 (1H, s), 6.62-6.70 (3H, m), 7.14-7.26 (4H, m), 7.30-7.35 (3H, m), 7.37-7.43 (3H, m). HPLC retention time: 1.19 min (method A). MS (ESI) (M+H)+ 439.22.

後処理

  1. temperatureat reflux for 3.5 h
  2. concentrationthe mixture was concentrated
  3. customto remove EtOH
  4. extractionthe mixture was extracted with ethyl acetate
  5. washthe organic phase was washed with sat. aqueous NaCl
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-4c586dc973bf48e3b04740b2e4cd3ce4
出典データセット
uspto-grants-2008_06
特許番号
US07388007B2

反応ノート

読み込み中…