Methyl iodide → 2-(1-(tert-Butyldimethylsilyloxy)-7-phenylheptyl)-5-methyloxazole

HRID 2386186Notes

Reaction equation

HRID 2386186 reaction equation
[Si:1]([O:8][CH:9]([C:22]1[O:23][CH:24]=[CH:25][N:26]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li][C:28](C)(C)C.CI>C1COCC1.CCOC(C)=O>[Si:1]([O:8][CH:9]([C:22]1[O:23][C:24]([CH3:28])=[CH:25][N:26]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 685237222-(1-{[tert-Butyl(dimethyl)silyl]oxy}-7-phenylheptyl)-1,3-oxazoleHCID 178418306HCID 178418306, compound

Product 1

HCID 685249672-(1-(tert-Butyldimethylsilyloxy)-7-phenylheptyl)-5-methyloxazoleYield 44%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

2-(1-(tert-Butyldimethylsilyloxy)-7-phenylheptyl)oxazole (166 mg, 0.444 mmol) was dissolved in anhydrous THF (4 mL), cooled to −78° C. and t-BuLi (1.7 M in pentane, 1.3 equiv) was added dropwise under Ar. The reaction mixture was stirred for 2 h at −40° C., cooled to −78° C. and methyl iodide (3 equiv) was added dropwise and stirred for 1 h. The reaction mixture was warmed to room temperature, diluted with EtOAc, washed with saturated aqueous NaCl and dried over Na2SO4. Evaporation in vacuo yielded the crude product, which was purified by flash chromatography (0-2% EtOAc/hexanes) to afford the title compound as a clear oil (76 mg, 44%): 1H NMR (CDCl3, 600 MHz) δ 7.28-7.25 (m, 2H), 7.17-7.16 (m, 3H), 6.64 (s, 1H), 4.72 (t, 1H, J=7.2 Hz), 2.59 (t, 2H, J=7.8 Hz), 2.29 (s, 3H), 1.90-1.82 (m, 2H), 1.62-1.59 (m, 2H), 1.43-1.34 (m, 6H), 0.88 (s, 9H), 0.08 (s, 3H), −0.04 (s, 3H); 13C NMR (CDCl3, 150 MHz) δ 164.9, 143.7, 139.3, 129.2, 129.1, 126.4, 123.2, 69.5, 37.2, 36.8, 32.3, 30.0, 26.6, 26.6, 26.0, 19.1, 11.7, −4.2, −4.3.

Workup

  1. temperaturecooled to −78° C.
  2. stirringstirred for 1 h
  3. temperatureThe reaction mixture was warmed to room temperature
  4. washwashed with saturated aqueous NaCl
  5. dry with materialdried over Na2SO4
  6. customEvaporation in vacuo
  7. customyielded the crude product, which
  8. customwas purified by flash chromatography (0-2% EtOAc/hexanes)

Sources & evidence

ORD record
ord-17027c24cdda485fa62d8f03617b6048
Source dataset
uspto-grants-2012_09
Patent number
US08268817B2

Reaction notes

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