Ethyl Acetate → Jnj-18038683

HRID 749890Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 749890
C([O:5]C([N:8]1[CH2:17][CH2:16][C:15]2[N:14]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:13]=[C:12]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.[C:32]([O-:35])([O-:34])=O.[Na+].[Na+].ClC1C=CC(B2[O:49][C:48]3[CH:50]=CC=C[C:47]=3[O:46]2)=CC=1.C(OC(N1CCC2N(CC3C=CC=CC=3)N=C(OS(C(F)(F)F)(=O)=O)C=2CC1)=O)(C)(C)C.CC[O:88][C:89]([CH3:91])=[O:90]>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[C:89]([OH:88])(=[O:90])[CH2:91][C:48]([CH2:50][C:32]([OH:35])=[O:34])([C:47]([OH:46])=[O:5])[OH:49].[CH2:18]([N:14]1[C:15]2[CH2:16][CH2:17][NH:8][CH2:9][CH2:10][C:11]=2[C:12]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)=[N:13]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Komponenten

10

Edukt 5

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 32553502-(4-Chlorophenyl)-1,3,2-benzodioxaboroleHCID 672688521-Benzyl-6-Boc-3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepineHCID 865983901-benzyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester

Produkt 1

HCID 11249539Jnj-18038683Ausbeute 92 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Versuchsvorschrift

1-Benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. To a 1-L, three-necked, round-bottomed flask was added Pd(dppf)Cl2 (2.8 g, 3.4 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.96 g, 1.73 mmol), Bu4N+Br− (2.78 g, 8.6 mmol), Na2CO3 (36.5 g, 344 mmol) and 2-(4-chloro-phenyl)-benzo[1,3,2]dioxaborole (23.8 g, 103 mmol), under N2. A solution of 1-benzyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (41 g, 86 mmol) in toluene (250 mL) was added, followed by the addition of H2O (250 mL) via syringe. The reaction mixture was stirred at reflux for 3 h and then was cooled to rt. The organic layer was diluted with EtOAc (200 mL) and then was washed with 1 M aq. K2CO3 until the color of the aqueous layer stabilized. The organic layer was washed with brine (200 mL), dried over MgSO4, filtered, and concentrated. The crude product thus obtained was pad-filtered through a short plug of SiO2 to afford the title compound (34.5, 79 mmol, 92%) as a white solid. MS (ESI): exact mass calculated for C25H28ClN3O2, 437.19; found, m/z 438.1, [M+H]+. HPLC (Method B): Rt=10.89 min. 1H NMR (400 MHz, CDCl3): 7.50-7.45 (m, 2H), 7.40-7.36 (m, 2H), 7.36-7.25 (m, 3H), 7.13-7.10 (m, 2H), 5.35-5.33 (m, 2H), 3.56-3.50 (m, 4H), 2.83-2.75 (m, 4H), 1.28-1.25 (m, 9H).

Aufarbeitung

  1. temperatureat reflux for 3 h
  2. washwas washed with 1 M aq. K2CO3 until the color of the aqueous layer
  3. washThe organic layer was washed with brine (200 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product thus obtained
  8. filtrationwas pad-filtered through a short plug of SiO2

Quellen und Nachweise

ORD-Eintrag
ord-776e182b5ea749838438471720a43996
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07402680B2

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