Methyl Acrylate → Methyl 4-(1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)butanoate

HRID 1855084Notes

Reaction equation

HRID 1855084 reaction equation
[C:1]([O:5][CH3:6])(=[O:4])[CH:2]=[CH2:3].I[CH2:8][C:9]12[CH2:16][CH2:15][C:12]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:18]=3)([CH2:13][CH2:14]1)[O:11][CH2:10]2>N1C=CC=CC=1.CCOC(C)=O.[Zn]>[O:23]([C:19]1[CH:18]=[C:17]([C:12]23[CH2:15][CH2:16][C:9]([CH2:8][CH2:3][CH2:2][C:1]([O:5][CH3:6])=[O:4])([CH2:14][CH2:13]2)[CH2:10][O:11]3)[CH:22]=[CH:21][CH:20]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 2

HCID 7294Methyl AcrylateHCID 904081314-(Iodomethyl)-1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octane

Product 1

HCID 90408543Methyl 4-(1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)butanoateYield 73%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 1049PyridineSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of Zn (622 mg, 9.52 mmol), anhydrous pyridine (5 mL) and methyl acrylate (0.95 mL, 9.52 mmol) was warmed to 50° C., after which NiCl2.6H2O (283 mg, 1.19 mmol) was added. The resulting mixture was heated to 65° C. for 1 h and stirred until the color of the solution became reddish-brown, then was cooled to 0° C., after which a solution of 4-(iodomethyl)-1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octane (500 mg, 1.190 mmol) in pyridine (2 mL) was added. The reaction mixture was allowed to warm to rt overnight, then was diluted with EtOAc (10 mL) and the resulting mixture was filtered off through a pad of CELITE®. The filtrate was washed with 1 N aq. HCl and brine, dried (MgSO4), and concentrated in vacuo. The residual crude oil was purified by flash chromatography (SiO2; gradient from 0 to 50% EtOAc:hexanes) to afford the title compound as a colorless oil (318 mg, 73% yield). LCMS, [M+H]+=381, 1H NMR (400M Hz, CDCl3) δ 7.39-7.24 (m, 3H), 7.19-7.06 (m, 3H), 7.04-6.98 (m, 2H), 6.86 (ddd, J=8.1, 2.4, 0.9 Hz, 1H), 3.82 (s, 2H), 3.70 (s, 3H), 2.31 (t, J=7.3 Hz, 2H), 2.10-1.98 (m, 4H), 1.76-1.57 (m, 6H), 1.22-1.12 (m, 2H).

Workup

  1. temperatureThe resulting mixture was heated to 65° C. for 1 h
  2. temperaturewas cooled to 0° C.
  3. temperatureto warm to rt overnight
  4. filtrationthe resulting mixture was filtered off through a pad of CELITE®
  5. washThe filtrate was washed with 1 N aq. HCl and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residual crude oil was purified by flash chromatography (SiO2; gradient from 0 to 50% EtOAc:hexanes)

Sources & evidence

ORD record
ord-d126beef61e04ff78d240c262f152235
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

Loading…