Hydrochloric Acid → tert-butyl ((3R,4S,5S)-1-(3-aminopyridin-4-yl)-4-azido-5-methylpiperidin-3-yl)carbamate

HRID 705311Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 705311
Cl.O1CCOCC1.[N:8]([C@H:11]1[C@@H:16]([CH3:17])[CH2:15][N:14]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][C:19]=2[N:24](C(OC(C)(C)C)=O)C(=O)OC(C)(C)C)[CH2:13][C@H:12]1[NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])=[N+:9]=[N-:10].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>C(Cl)Cl>[NH2:24][C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:18]=1[N:14]1[CH2:15][C@H:16]([CH3:17])[C@H:11]([N:8]=[N+:9]=[N-:10])[C@H:12]([NH:39][C:40](=[O:41])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:13]1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 90495Di-tert-butyl dicarbonateHCID 86705280tert-butyl (4-((3R,4S,5S)-4-azido-3-((tert-butoxycarbonyl)amino)-5-methylpiperidin-1-yl)pyridin-3-yl)(tert-butoxycarbonyl)carbamate

Produkt 1

HCID 86705282tert-butyl ((3R,4S,5S)-1-(3-aminopyridin-4-yl)-4-azido-5-methylpiperidin-3-yl)carbamateAusbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 4 M HCl in dioxane (30.0 equiv.) was added to tert-butyl (4-((3R,4S,5S)-4-azido-3-((tert-butoxycarbonyl)amino)-5-methylpiperidin-1-yl)pyridin-3-yl)(tert-butoxycarbonyl)carbamate (1.0 equiv.). The solution started to go homogeneous for a few minutes, but then a ppt formed and the solution went very thick. After sitting at rt for 1 hour, the volatiles were removed in vacuo and the solid was pumped on for 5 minutes on the high vac. To the residue was added CH2Cl2 (0.11 M), TEA (5.0 equiv.) and Boc2O (1.0 equiv.). The solution was left stirring at rt for 1 hr. The volatiles were removed in vacuo and the residue was partitioned between EtOAc and H2O. The organic layer was washed with Na2CO3(sat), NaCl(sat.), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography to yield tert-butyl ((3R,4S,5S)-1-(3-aminopyridin-4-yl)-4-azido-5-methylpiperidin-3-yl)carbamate in 33% yield. LC/MS (m/z)=348.2 (MH+), Rt=0.70 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.02-1.18 (m, 3 H), 1.36-1.54 (m, 10 H), 2.19 (qd, J=6.91, 3.91 Hz, 1 H), 2.57 (q, J=10.96 Hz, 2 H), 2.96 (d, J=9.00 Hz, 1 H), 3.20 (dd, J=11.15, 3.72 Hz, 1 H), 3.55-3.73 (m, 2 H), 3.90 (br. s., 1 H), 4.01 (br. s., 1 H), 4.81 (d, J=8.61 Hz, 1 H), 6.72-6.83 (m, 1 H), 7.96 (d, J=5.09 Hz, 1 H), 8.02 (s, 1 H).

Aufarbeitung

  1. waitto go homogeneous for a few minutes
  2. customa ppt formed
  3. customthe volatiles were removed in vacuo
  4. customwas pumped on for 5 minutes on the high vac
  5. waitThe solution was left
  6. customThe volatiles were removed in vacuo
  7. customthe residue was partitioned between EtOAc and H2O
  8. washThe organic layer was washed with Na2CO3(sat), NaCl(sat.)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified by ISCO SiO2 chromatography

Quellen und Nachweise

ORD-Eintrag
ord-cbc718ea89a24963b3f3af7834ea6742
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09173883B2

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