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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
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HRID 1911847 반응식
[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]
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참가 물질

7

반응물 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

생성물 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 acid수율 96%

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-dbd5b7a57dde4b7196fb3fbf297450be
출처 데이터셋
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08604038B2

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