Methyl Acrylate → Methyl 4-(1-(2-methyl-4-phenylthiazol-5-yl)-2-oxabicyclo[2.2.2]octan-4-yl)butanoate

HRID 1855034Notes

Reaction equation

HRID 1855034 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[S:21][C:20]([CH3:22])=[N:19][C:18]=3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)([CH2:13][CH2:14]1)[O:11][CH2:10]2>N1C=CC=CC=1.CCOC(C)=O.[Zn]>[CH3:22][C:20]1[S:21][C:17]([C:12]23[CH2:13][CH2:14][C:9]([CH2:8][CH2:3][CH2:2][C:1]([O:5][CH3:6])=[O:4])([CH2:16][CH2:15]2)[CH2:10][O:11]3)=[C:18]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:19]=1

Participants

6

Reactant 2

HCID 7294Methyl AcrylateHCID 904086535-(4-(Iodomethyl)-2-oxabicyclo[2.2.2]octan-1-yl)-2-methyl-4-phenylthiazole

Product 1

HCID 90408210Methyl 4-(1-(2-methyl-4-phenylthiazol-5-yl)-2-oxabicyclo[2.2.2]octan-4-yl)butanoateYield 85%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 1049PyridineSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of zinc powder (154 mg, 2.351 mmol), anhydrous pyridine (5 mL) and methyl acrylate (0.212 ml, 2.351 mmol) at 50° C. was added NiCl2.6H2O (56 mg, 0.235 mmol). The resulting mixture was warmed to 75° C. and stirred for 2 h until its green color turned to reddish brown. After cooling to 0° C., a solution of 5-(4-(iodomethyl)-2-oxabicyclo[2.2.2]octan-1-yl)-2-methyl-4-phenylthiazole (100 mg, 0.235 mmol) in anhydrous pyridine (3 mL) was added and the reaction mixture was stirred for 2 h at room temperature. The mixture was diluted with EtOAc (10 mL) and the resulting precipitate was filtered off through a pad of CELITE®. The filtrate was washed with 1 N aqueous HCl and brine, dried (Na2SO4), and concentrated in vacuo to afford the title compound (77 mg, 85% yield) as a clear oil. LCMS, [M+H]+=386.0. 1H NMR (500 MHz, CDCl3) δ 7.46-7.40 (m, 2H), 7.40-7.32 (m, 3H), 3.72 (s, 2H), 3.65 (s, 3H), 2.64 (s, 3H), 2.24 (t, J=7.4 Hz, 2H), 2.07-1.97 (m, 2H), 1.87-1.77 (m, 2H), 1.57-1.45 (m, 6H), 1.12-1.02 (m, 2H).

Workup

  1. temperatureAfter cooling to 0° C.
  2. stirringthe reaction mixture was stirred for 2 h at room temperature
  3. filtrationthe resulting precipitate was filtered off through a pad of CELITE®
  4. washThe filtrate was washed with 1 N aqueous HCl and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a6b6aee89ab442a88823b5018d19d471
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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