Tert-Butylamine → Tert-butyl 5-formyl-6-azaspiro[2.5]octane-6-carboxylate

HRID 536580

Reaktionsgleichung

Reaktionsgleichung von HRID 536580
COC(=O)[CH2:4][C@H:5]([N:9]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:10][CH2:11][C:12](OC)=O)[C:6]([OH:8])=O.C[O-].[Na+].CO.[C:29](N)(C)(C)[CH3:30]>C1COCC1>[CH:6]([CH:5]1[N:9]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:10][CH2:11][C:12]2([CH2:30][CH2:29]2)[CH2:4]1)=[O:8]

Komponenten

5

Edukt 3

HCID 6385Tert-ButylamineHCID 10936520(S)-2-[tert-butoxycarbonyl-(2-methoxycarbonyl-ethyl)-amino]-succinic acid 4-methyl ester2×HCID 23694274Sodium methanolate methanol

Produkt 1

HCID 86664865Tert-butyl 5-formyl-6-azaspiro[2.5]octane-6-carboxylateAusbeute 55,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a solution of (S)-2-[tert-Butoxycarbonyl-(2-methoxycarbonyl-ethyl)-amino]-succinic acid 4-methyl ester (intermediate 12, 420 g, 1.35 mol) in THF (2 L) under nitrogen cooled to 0° C. was added NaOMe/MeOH (1.5 L, 2.7M) in half an hour. The resulting yellow solution was stirred at 85° C. for 3 hours (after 1 hour a suspension was obtained). THF (1.5 L) was distilled off under the reduced pressure and water (2 L) was added. The resulting mixture was stirred at 110° C. for 20 hours. The mixture was washed with ethyl acetate (2×1 L). The aqueous solution was cooled to 0° C. and the value of pH was adjusted to 2.5 with concentrated HCl. The product was extracted with ethyl acetate (3×1 L) and the organic extracts were combined, washed with saturated NaCl (1 L), dried (Na2SO4) and filtered. The filtrate was cooled to 0° C. and tert-butylamine (145 ml, 1.35 mol) was added with stirring. The yellow solid was collected by filtration and dried, then boiled in isopropyl alcohol (1.5 L). The suspension was cooled to 5° C. and collected by filtration to give 180 g of intermediate 3 (light white solid, yield:45%).

Aufarbeitung

  1. customwas obtained)
  2. distillationTHF (1.5 L) was distilled off under the reduced pressure and water (2 L)
  3. additionwas added
  4. stirringThe resulting mixture was stirred at 110° C. for 20 hours
  5. washThe mixture was washed with ethyl acetate (2×1 L)
  6. temperatureThe aqueous solution was cooled to 0° C.
  7. extractionThe product was extracted with ethyl acetate (3×1 L)
  8. washwashed with saturated NaCl (1 L)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. temperatureThe filtrate was cooled to 0° C.
  12. stirringwith stirring
  13. filtrationThe yellow solid was collected by filtration
  14. customdried
  15. temperatureThe suspension was cooled to 5° C.
  16. filtrationcollected by filtration

Quellen und Nachweise

ORD-Eintrag
ord-2f4ec597ed5948fe8457c8b86be28fb3
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08859608B2

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