تفاعل #80989

ord-5bbb6b6aa3e04b238f75525318c0cacd

المذيبات

ظروف التفاعل

درجة الحرارة
-78°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىPrepared
  2. 2
    درجة الحرارةto warm to -30° C. over the next 2 hrs
  3. 3
    workup.STIRRINGthe reaction was then stirred at 0° C. for 30 mins
  4. 4
    أخرىThe reaction was quenched at 0° C. with glacial HoAc (4.22 g, 0.0702 mol)
  5. 5
    أخرىthe solvent was removed by rotary evaporation in vacuo
  6. 6
    أخرىThe golden solid was partitioned with H2O (45 mL) and EtOAc (200 mL)
  7. 7
    استخلاصthe aqueous extracted with EtOAc (2×200 mL)
  8. 8
    غسيلThe combined organic was washed with satd aq NaCl
  9. 9
    تجفيفdried over Na2SO4
  10. 10
    تركيزconcentrated in vacuo to a brown oil

الإجراء التجريبي

Prepared according to the procedure of Schollkopf (J. Am. Chem. Soc. 112 (10) 4070 (1990)). To a solution of methyl isocyanide (2.88 g, 0.0702 mol) in THF (50 mL) under argon at -78° C. was added dropwise n-butyllithium solution (1.6M in hexanes, 44 mL) over 15 mins. After stirring for an additional 20 mins at -78° C., a solution of ethyl diethoxyacetate (12.62 g, 0.0702 mol) in THF (15 mL) was added dropwise over 20 mins. The bath was allowed to warm to -30° C. over the next 2 hrs and the reaction was then stirred at 0° C. for 30 mins. The reaction was quenched at 0° C. with glacial HoAc (4.22 g, 0.0702 mol) and the solvent was removed by rotary evaporation in vacuo. The golden solid was partitioned with H2O (45 mL) and EtOAc (200 mL), and the aqueous extracted with EtOAc (2×200 mL). The combined organic was washed with satd aq NaCl, dried over Na2SO4, and concentrated in vacuo to a brown oil. Chromatography on a 300 g SiO2 flash column with a gradient of EtOAc/hexane (10%, 15%, 20%) afforded the desired compound as a colorless liquid (7.46 g, 0.0436 mol, 62%): 1H NMR (CDCl3) δ1.25 (t, J=6.9 Hz, 6H), 3.56-3.70 (m, 4H), 5.62 (s, 1H), 7.26 (s, 1H), 7.86 (s, 1H). Mass spectrum: (M+H)+ =172.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US05616720uspto-grants-1997_04