Hydrochloric Acid → Ammonia

HRID 1433282ノート

反応式

HRID 1433282 の反応式
C(OC(=O)[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[C:21]([C@@H:33]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH2:34][CH2:35][N:36]([CH:40]([CH3:42])[CH3:41])[CH:37]([CH3:39])[CH3:38])[CH:20]=2)=[CH:12][CH:11]=1)(C)(C)C.Cl.[CH2:51]([O:58][C:59]1[CH:64]=[CH:63][C:62]([C@@H:65]([O:68][Si:69]([C:72]([CH3:75])([CH3:74])[CH3:73])([CH3:71])[CH3:70])[CH2:66]Br)=[CH:61][C:60]=1[CH2:76][OH:77])[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1.C(=O)([O-])O.[Na+]>O1CCOCC1.O.C(OCC)(=O)C>[NH3:7].[CH2:51]([O:58][C:59]1[CH:64]=[CH:63][C:62]([C@@H:65]([O:68][Si:69]([C:72]([CH3:75])([CH3:74])[CH3:73])([CH3:71])[CH3:70])[CH2:66][NH:7][CH2:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)=[C:21]([C@@H:33]([C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[CH2:34][CH2:35][N:36]([CH:37]([CH3:39])[CH3:38])[CH:40]([CH3:42])[CH3:41])[CH:20]=3)=[CH:14][CH:15]=2)=[CH:61][C:60]=1[CH2:76][OH:77])[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1

参加物

9

反応物 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 12988834[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanolHCID 57933204tert-butyl {2-[4-(2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethoxy)phenyl]ethyl}carbamate

生成物 2

HCID 222AmmoniaHCID 57933171{2-(benzyloxy)-5-[(1R)-2-({2-[4-(2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethoxy)phenyl]ethyl}amino)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanol

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

tert-butyl{2-[4-(2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethoxy)phenyl]ethyl}carbamate (Preparation 41, 830 mg, 1.25 mmol) was treated with hydrochloric acid (8 ml of a 4M solution in 1,4-dioxane) and stirred at room temperature overnight, and the solvent was removed in vacuo. The residue was dissolved in acteonitrile (8 ml) and {2-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanol (Sali patent, 560 mg, 1.24 mmol) and sodium hydrogen carbonate (368 mg, 4.34 mmol) added. Mixture heated to 85° C. and stirred overnight. Reaction was cooled to room temperature and ethyl acetate and water added, the aqueous layer was separated and washed with ethyl acetate and the combined organics dried (magnesium sulphate) and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (92.517.511 by volume) to furnish the title compound as a gum, 280 mg.

後処理

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in acteonitrile (8 ml)
  3. temperatureMixture heated to 85° C.
  4. stirringstirred overnight
  5. customReaction
  6. temperaturewas cooled to room temperature
  7. customthe aqueous layer was separated
  8. washwashed with ethyl acetate
  9. dry with materialthe combined organics dried (magnesium sulphate)
  10. customthe solvent removed in vacuo
  11. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

出典と根拠

ORDレコード
ord-53c0b75beba049ccb718e3d771d60a80
出典データセット
uspto-grants-2009_11
特許番号
US07612084B2

反応ノート

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