(5-Carboxypentyl)triphenylphosphanium bromide → (4S)-(E)-7-[4-[4-[[(4-Cyclohexylbutyl)amino]carbonyl]-4,5-dihydro-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic Acid

HRID 378739

Reaktionsgleichung

Reaktionsgleichung von HRID 378739
[Br-].C(CCCCC[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)(O)=O.CC([O-])(C)C.[K+].CO.CC(O)=O.C(Cl)Cl.[CH:44]1([CH2:50][CH2:51][CH2:52][CH2:53][NH:54][C:55]([C:57]([NH:59][C:60]([C:62]2[CH:67]=[CH:66][C:65](/[C:68](/[C:77]3[CH:78]=[N:79][CH:80]=[CH:81][CH:82]=3)=[CH:69]\[CH2:70][CH2:71][CH2:72][CH2:73][C:74]([OH:76])=[O:75])=[CH:64][CH:63]=2)=[O:61])=[CH2:58])=[O:56])[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1>C1COCC1>[CH:44]1([CH2:50][CH2:51][CH2:52][CH2:53][NH:54][C:55]([C@@H:57]2[CH2:58][O:61][C:60]([C:62]3[CH:63]=[CH:64][C:65](/[C:68](/[C:77]4[CH:78]=[N:79][CH:80]=[CH:81][CH:82]=4)=[CH:69]\[CH2:70][CH2:71][CH2:72][CH2:73][C:74]([OH:76])=[O:75])=[CH:66][CH:67]=3)=[N:59]2)=[O:56])[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1

Komponenten

6

Edukt 4

HCID 2779280(5-Carboxypentyl)triphenylphosphanium bromideHCID 21877243DCM MeOH AcOHHCID 23665647Potassium tert-butoxideHCID 44366527(E)-7-{4-[1-(4-Cyclohexyl-butylcarbamoyl)-vinylcarbamoyl]-phenyl}-7-pyridin-3-yl-hept-6-enoic acid

Produkt 1

HCID 15852311(4S)-(E)-7-[4-[4-[[(4-Cyclohexylbutyl)amino]carbonyl]-4,5-dihydro-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic AcidAusbeute 38 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Using the method described above at example 18-G, 1.472 g (3.4 mmol) of (4S)-4,5-dihydro-2-[4-(3-pyridylcarbonyl)phenyl]oxazole-4-[N-(4-cyclohexylbutyl)]-L-serinamide was treated with 3.08 g (6.8 mmol) of (5-carboxypentyl)triphenylphosphonium bromide and 13.6 mL (13.6 mmol) of 1.0 M t-BuOK in 10.0 mL of THF at 0° C. for 2.5 hr. Preparative HPLC with MeOH-AcOH-CH2Cl2 (3:0.5:96.5) yielded ~700 mg (38%) of the title product and ~670 mg (37%) of the β-elimination Wittig product (less polar material) (E)-7-[4-[[[1-[[(4-cyclohexylbutyl)amino]carbonyl]-eth-1-enyl]amino]carbonyl]phenyl]-7-(3-pyridyl)-hept-6-enoic acid (311030): mp 61-63° C.; 1H NMR (CDCl3) δ9.05 (s, 1H), 8.58 (s, 1H), 8.48 (d, J=3.3 Hz, 1H), 7.89 (d, J=8.2 Hz, 2H), 7.43 (br d, J=8.0 Hz, 1H), 7.26 (d, J=8.0 Hz, 2H), 7.25 (buried, 1H), 6.63 (d, J=1.1 Hz, 1H), 6.55 (br s, 1H), 6.21 (t, J=7.4 Hz, 1H), 5.35 (s, 1H), 3.37 (dt, J=6.8, 6.3 Hz, 2H), 2.32 (dd, J=7.1, 6.9 Hz, 2H), 2.18 (ddd, J=7.3, 7.2, 7.1 Hz, 2H), 1.69-0.83 (m, 21H); FDMS 532 (M+1). Anal. (C32H41N3O4) C, H, N.

Quellen und Nachweise

ORD-Eintrag
ord-f3ebc73bcbb140b9a6e52abcc6f2b1e4
Quelldatensatz
uspto-grants-2000_02
Patentnummer
US06031095

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