Hydrochloric Acid → Benzyl 4-((tert-butoxycarbonyl)amino)piperidine-1-carboxylate

HRID 451298

Reaktionsgleichung

Reaktionsgleichung von HRID 451298
[C:1]([NH:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CC)CC)C.Cl[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24].Cl>C(Cl)Cl>[C:4]([O:3][C:1]([NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[CH2:11][CH2:10]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 7238334-(N-Boc-amino)piperidine

Produkt 1

HCID 21981786Benzyl 4-((tert-butoxycarbonyl)amino)piperidine-1-carboxylateAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

4-(N—BOC amino) piperidine (17 kg, 84.88 mol) was dissolved in DCM (90 kg), triethylamine (10.14 kg, 100.16 mol) was added, and the resulting solution was cooled to 0-5° C. Benzyl chloroformate (16.51 kg, 96.76 mol) was added over 45 minutes while keeping the temperature at <25° C., after which the solution was aged for 30 minutes at 20° C. 2 M HCl (61 kg, 118.13 mol) was then added over 10 minutes while keeping the temperature at <25° C. The mixture was agitated for 10 minutes and then the agitation was stopped and the phases were allowed to separate. The phases were then separated from each other, and the organic phase was distilled in vacuo to a volume of 35 L. Isopropyl acetate (89 kg) was then added, and the batch was concentrated by vacuum distillation at less than 35° C. to a volume of 50 L to crystallize the title product. Heptane (47 kg) was then added over 10 minutes, and the resulting slurry cooled to and aged at 20° C. for 20 minutes, after which the aged slurry was filtered, washed with heptane (17 kg), and dried by N2 sweep on the filter to give the title product as a white solid (24.7 kg, 87%). 1H NMR (CDCl3) 7.33 (5H, m), 5.13 (2H, s), 4.47 (1H, m), 4.11 (2H, m), 3.61 (1H, m), 2.93 (2H, m), 1.94 (2H, m), 1.45 (9H, s) and 1.30 (2H, m).

Aufarbeitung

  1. customat <25° C.
  2. customat <25° C
  3. customto separate
  4. customThe phases were then separated from each other, and the organic phase
  5. distillationwas distilled in vacuo to a volume of 35 L
  6. additionIsopropyl acetate (89 kg) was then added
  7. concentrationthe batch was concentrated by vacuum distillation at less than 35° C. to a volume of 50 L
  8. customto crystallize the title product
  9. additionHeptane (47 kg) was then added over 10 minutes
  10. temperaturethe resulting slurry cooled to and
  11. waitaged at 20° C. for 20 minutes
  12. filtrationafter which the aged slurry was filtered
  13. washwashed with heptane (17 kg)
  14. dry with materialdried by N2 sweep on the
  15. filtrationfilter

Quellen und Nachweise

ORD-Eintrag
ord-ea4f8fce1f374caaafdc054cb36f1083
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08487093B2

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