Triphenylphosphine → 1-[(S)-1-(4-Methoxy-phenyl)-ethyl]-(R)-4-[(R)-1-[7-(3,4,5-trimethoxy-phenyl)-[1,6]naphthyridin-5-yloxy]-ethyl]-pyrrolidin-2-one

HRID 870555

Reaktionsgleichung

Reaktionsgleichung von HRID 870555
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[N:14]=[C:15]([OH:23])[C:16]3[CH:17]=[CH:18][CH:19]=[N:20][C:21]=3[CH:22]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].O[C@H:25]([C@H:27]1[CH2:31][N:30]([C@H:32]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[CH3:33])[C:29](=[O:42])[CH2:28]1)[CH3:26].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[CH3:41][O:40][C:37]1[CH:38]=[CH:39][C:34]([C@@H:32]([N:30]2[CH2:31][C@H:27]([C@H:25]([O:23][C:15]3[N:14]=[C:13]([C:5]4[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=4)[CH:22]=[C:21]4[C:16]=3[CH:17]=[CH:18][CH:19]=[N:20]4)[CH3:26])[CH2:28][C:29]2=[O:42])[CH3:33])=[CH:35][CH:36]=1

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 58071870(R)-4-((S)-1-hydroxyethyl)-1-((S)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-oneHCID 178487380HCID 178487380, Verbindung

Produkt 1

HCID 580720441-[(S)-1-(4-Methoxy-phenyl)-ethyl]-(R)-4-[(R)-1-[7-(3,4,5-trimethoxy-phenyl)-[1,6]naphthyridin-5-yloxy]-ethyl]-pyrrolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

114.6 g of powdered 7-(3,4,5-trimetoxy-phenyl)-[1.6]naphthyridine-5-ol is suspended in 900 mL tetrahydrofurane. A solution of 115.9 g of (R)-4-[(S)-1-hydroxyethyl]-1-[(S)-1-(4-methoxyphenyl)-ethyl]-pyrrolidin-2-one and 136 g triphenylphosphine in 1000 mL tetrahydrofurane is added. The suspension is cooled to 0° C. During 40 minutes a solution of 105 mL diisopropylazodicarboxylate [DIAD] in 400 mL tetrahydrofurane is added at 0° C. to 2° C. The suspension is stirred for 3.5 hours at this temperature and then warmed up to 20° C. The solvent is evaporated under reduced pressure. The residue is suspended in 680 mL of tert-butylmethylether. Seeding crystalls of triphenylphosphinoxid are added and the mixture is stirred 16 hours at 20° C. The precipitate is filtered and and washed with tert.-butylmethylether. The fitrate is evaporated under reduced pressure. The crude product is dissolved in a mixture of 220 mL of 2-propanol and 1100 mL of isopropyl acetate at 40° C. 48 mL of trimethylchlorosilane are added during 15 minutes. The suspension is stirred for 2 hours at 20° C. The precipitate is filtered and washed with isopropyl acetate and dried at 60

Aufarbeitung

  1. temperaturewarmed up to 20° C
  2. customThe solvent is evaporated under reduced pressure
  3. additionSeeding crystalls of triphenylphosphinoxid are added
  4. stirringthe mixture is stirred 16 hours at 20° C
  5. filtrationThe precipitate is filtered
  6. washwashed with tert.-butylmethylether
  7. customThe fitrate is evaporated under reduced pressure
  8. dissolutionThe crude product is dissolved in a mixture of 220 mL of 2-propanol and 1100 mL of isopropyl acetate at 40° C
  9. addition48 mL of trimethylchlorosilane are added during 15 minutes
  10. stirringThe suspension is stirred for 2 hours at 20° C
  11. filtrationThe precipitate is filtered
  12. washwashed with isopropyl acetate
  13. customdried at 60

Quellen und Nachweise

ORD-Eintrag
ord-f26f0af4be5f480b91fadee15200f115
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969568B2

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