Reaktion #1858923

Reaktionsgleichung

Iodomethane

2,2,6,6-tetramethylpiperidine

sec-BuLi

tert-butyl N-tert-butoxycarbonyl-N-(3-bromo-6-fluoro-2-methylphenyl)carbamate

NH4Cl

→

title compound

Ausbeute 85.2%

Tert-butyl N-tert-butoxycarbonyl-N-(3-bromo-6-fluoro-2,5-dimethylphenyl)carbamate

Ausbeute 85.2%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction was stirred a further 2 h at −65° C
2. 2
   Temperaturto warm to −10° C. over 30 min
3. 3
   Extraktionextracted with EtOAc
4. 4
   WaschenThe combined organic extracts were washed with brine
5. 5
   Trocknendried (Na2SO4)
6. 6
   Filtrationfiltered
7. 7
   Sonstigeevaporated in vacuo
8. 8
   Sonstigeto give a crude residue, which
9. 9
   Sonstigewas purified by column chromatography (petroleum ether:EtOAc, 100:0 to 30:1)

Vorschrift

To a stirred solution of 2,2,6,6-tetramethylpiperidine (699 mg, 4.9 mmol, 2.0 eq) in THF (7.5 mL) at −50° C. was added sec-BuLi (3.8 mL, 1.3 M, 4.9 mmol, 2.0 eq) dropwise. The reaction was stirred for 20 min at −15° C. to −10° C., then cooled to −65° C. and a solution of tert-butyl N-tert-butoxycarbonyl-N-(3-bromo-6-fluoro-2-methylphenyl)carbamate (See example 13) (1 g, 2.47 mmol, 1.0 eq) in THF (7.5 mL) added dropwise. The reaction was stirred a further 2 h at −65° C. Iodomethane (1.05 g, 7.41 mmol, 3.0 eq) was added in one portion and the reaction allowed to warm to −10° C. over 30 min. The reaction was then poured into saturated aqueous NH4Cl and extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4) filtered and evaporated in vacuo to give a crude residue, which was purified by column chromatography (petroleum ether:EtOAc, 100:0 to 30:1) to give the title compound as a white solid (880 mg, 85%).

Quelle