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Acetic Acid → 4-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]pyrrolidin-2-yl}methyl)benzoic acid

HRID 1911847
ノート
印刷プレビュー

反応式

HRID 1911847 の反応式
[Si:1]([O:8][C@H:9]([C:33]1[CH:34]=[N:35][C:36]([NH:39][C:40]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)([CH3:42])[CH3:41])=[CH:37][CH:38]=1)[C@H:10]1[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([O:24]C)=[O:23])=[CH:18][CH:17]=2)[N:11]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li+].[OH-].C(O)(=O)C>O1CCOCC1.O.CCOC(C)=O>[C:29]([O:28][C:26]([N:11]1[C@@H:10]([C@H:9]([O:8][Si:1]([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2])[C:33]2[CH:34]=[N:35][C:36]([NH:39][C:40]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)([CH3:41])[CH3:42])=[CH:37][CH:38]=2)[CH2:14][CH2:13][C@H:12]1[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]([OH:24])=[O:23])=[CH:20][CH:21]=1)=[O:27])([CH3:30])([CH3:31])[CH3:32]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 176Acetic AcidHCID 3939Lithium HydroxideHCID 86670464tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate

生成物 1

HCID 706558174-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]pyrrolidin-2-yl}methyl)benzoic acid収率 96%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a solution of tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate (0.340 g, 0.504 mmol) in dioxane (8 mL) and water (2 mL) was added 1M LiOH (1.51 mL, 1.51 mmol). The reaction was stirred vigorously at room temperature for 18 hours and then quenched with acetic acid (0.116 mL, 2.018 mmol). The reaction was diluted with EtOAc (125 mL) and washed with water (20 mL) and brine (20 mL). The organic extracts were dried over Na2SO4, filtered, and concentrated. The residue was taken up in CH2Cl2/heptanes and concentrated in vacuo to afford 4-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]pyrrolidin-2-yl}methyl)benzoic acid (319 mg, 96%). LC-MS=660.4 (M+1)+. 1H NMR (600 MHz, CD3OD) δ 7.90 (d, J=7.2 Hz, 2H), 7.79 (bs, 1H), 7.37 (bs, 2H), 7.28 (m, 1H), 7.02-7.12 (m, 5H), 6.13 (m, 1H), 5.31 & 5.12 (2 singlets, 1H), 4.00 (m, 1H), 3.84 (bs, 1H), 2.76 & 2.49 (2 multiplets, 1H), 1.14-1.96 (m, 20H), 0.88 (s, 9H), 0.08 (s, 3H), −0.06 (s, 3H).

後処理

  1. washwashed with water (20 mL) and brine (20 mL)
  2. dry with materialThe organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-dbd5b7a57dde4b7196fb3fbf297450be
出典データセット
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08604038B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート