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

HRID 1855101Notes

Reaction equation

HRID 1855101 reaction equation
[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]

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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%)

Sources & evidence

ORD record
ord-dab86a0654614fef96505050fe92ae52
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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