Pyridine → tert-Butyl 2-(2-(1-(3-(3-(tert-butyldimethylsilyloxy)phenoxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethoxy)acetate

HRID 1855101Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1855101
[OH:1][C:2]1[CH:3]=[C:4]([C:8]23[CH2:15][CH2:14][C:11]([CH2:16][CH2:17][O:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])([CH2:12][CH2:13]2)[CH2:10][O:9]3)[CH:5]=[CH:6][CH:7]=1.[Si:27]([O:34][C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].CCN(CC)CC.N1C=CC=CC=1.CC1C=CC(S(OCC23CCC(C4SC(C)=NC=4C4C=CC=CC=4)(CC2)OC3)(=O)=O)=CC=1>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Cu+2]>[Si:27]([O:34][C:35]1[CH:36]=[C:37]([CH:38]=[CH:39][CH:40]=1)[O:1][C:2]1[CH:3]=[C:4]([C:8]23[CH2:13][CH2:12][C:11]([CH2:16][CH2:17][O:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])([CH2:14][CH2:15]2)[CH2:10][O:9]3)[CH:5]=[CH:6][CH:7]=1)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]

Komponenten

8

Edukt 5

HCID 1049PyridineHCID 8471TriethylamineHCID 34630293-(tert-Butyldimethylsilyloxy)phenylboronic AcidHCID 90408312tert-Butyl 2-(2-(1-(3-hydroxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethoxy)acetateHCID 90408478(1-(2-Methyl-4-phenylthiazol-5-yl)-2-oxabicyclo[2.2.2]octan-4-yl)methyl 4-methylbenzenesulfonate

Produkt 1

HCID 90452492tert-Butyl 2-(2-(1-(3-(3-(tert-butyldimethylsilyloxy)phenoxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethoxy)acetateAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8895Cupric acetateKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of Example 7F compound [tert-butyl 2-(2-(1-(3-hydroxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethoxy)acetate] (350 mg, 0.97 mmol), (3-((tert-butyldimethylsilyl)oxy)phenyl)boronic acid (244 mg, 0.97 mmol), Cu(OAc)2 (144 mg, 0.97 mmol), Et3N (98 mg, 0.97 mmol) and pyridine (76 mg, 0.97 mmol) with 4A molecular sieves (1 g) in DCM (10 mL) was stirred at rt for 4 days. The reaction was then filtered, and the filtrate was concentrated in vacuo. The crude product was dissolved in EtOAc (5 mL) and washed with 1N aq. HCl and water, dried (MgSO4), and filtered. The filtrate was concentrated in vacuo and chromatographed (SiO2; continuous gradient of EtOAc/hexanes from 0-40%) to afford the title compound as a light yellow oil (380 mg, 69%). 1H NMR (400 MHz, CDCl3) δ 7.08-7.05 (m, 1H), 7.01-6.93 (m, 2H), 6.93-6.89 (m, 1H), 6.66 (ddd, J=8.1, 2.5, 1.1 Hz, 1H), 6.43-6.37 (m, 2H), 6.31 (t, J=2.3 Hz, 1H), 3.76 (s, 2H), 3.67 (s, 2H), 3.38 (t, J=7.0 Hz, 2H), 1.87 (s, 2H), 1.83 (dd, J=10.7, 5.4 Hz, 4H), 1.62-1.49 (m, 4H), 1.31 (s, 9H), 0.81-0.77 (m, 9H), 0.02-−0.02 (m, 6H).

Aufarbeitung

  1. filtrationThe reaction was then filtered
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe crude product was dissolved in EtOAc (5 mL)
  4. washwashed with 1N aq. HCl and water
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customchromatographed (SiO2; continuous gradient of EtOAc/hexanes from 0-40%)

Quellen und Nachweise

ORD-Eintrag
ord-dab86a0654614fef96505050fe92ae52
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962660B2

Notizen zur Reaktion

Wird geladen…