Triphenylphosphine → (S)-2-({(3S,8S)-7-Benzoyl-3-[4-(3,3-dimethyl-butoxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid

HRID 708743

Reaktionsgleichung

Reaktionsgleichung von HRID 708743
C[O:2][C:3](=[O:52])[C@@H:4]([NH:20][C:21]([C@@H:23]1[CH2:32][C:31]2[CH:30]=[C:29]3[O:33][CH2:34][C@H:35]([C:37]4[CH:42]=[CH:41][C:40](O)=[CH:39][CH:38]=4)[O:36][C:28]3=[CH:27][C:26]=2[CH2:25][N:24]1[C:44](=[O:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[C:13]=2[CH3:19])=[CH:8][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:72][C:73]([CH3:78])([CH3:77])[CH2:74][CH2:75][OH:76].CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[C:44]([N:24]1[C@H:23]([C:21]([NH:20][C@@H:4]([CH2:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]3[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[C:13]=3[CH3:19])=[CH:8][CH:7]=2)[C:3]([OH:52])=[O:2])=[O:22])[CH2:32][C:31]2[CH:30]=[C:29]3[O:33][CH2:34][C@H:35]([C:37]4[CH:42]=[CH:41][C:40]([O:76][CH2:75][CH2:74][C:73]([CH3:78])([CH3:77])[CH3:72])=[CH:39][CH:38]=4)[O:36][C:28]3=[CH:27][C:26]=2[CH2:25]1)(=[O:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 122333,3-Dimethyl-1-butanolHCID 5363146Diisopropyl azodicarboxylateHCID 58327345(S)-2-{[(3S,8S)-7-Benzoyl-3-(4-hydroxy-phenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester

Produkt 1

HCID 58327144(S)-2-({(3S,8S)-7-Benzoyl-3-[4-(3,3-dimethyl-butoxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(S)-2-{[(3S,8S)-7-Benzoyl-3-(4-hydroxy-phenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester (18 mg) was dissolved in DCM, triphenyl phosphine (5.9 eq.). 3,3-Dimethyl-butan-1-ol (excess) added and mixture cooled on ice. DIAD (5.1 eq.) was added and the reaction mixture stirred on ice for 10 minutes and rt for 16 hours. The reaction mixture was directly purified over silica (DCM-EtOAc 8:2 to DCM-EtOAc 6:4). The resulting residue was hydrolyzed according to General Procedure B and purified over silica (DCM to DCM+1% MeOH to DCM+7% MeOH) to give the title compound (11 mg). LCMS (m/z): 769.

Aufarbeitung

  1. temperaturemixture cooled on ice
  2. customThe reaction mixture was directly purified over silica (DCM-EtOAc 8:2 to DCM-EtOAc 6:4)
  3. custompurified over silica (DCM to DCM+1% MeOH to DCM+7% MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-87fbe8cf09e5444fb0d52d04756771cf
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09175003B2

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