反应详情

A solution of butyllithium, 2.5M in hexanes (1.718 mL, 4.30 mmol) was added dropwise to a solution of 2,2,6,6-tetramethylpiperidine (0.802 mL, 4.73 mmol) in 15 ml THF at −78° C. The flask was removed from the −78° C. bath, and stirred at ca 0° C. for 10 minutes, then recooled to −78° C. to give a pale yellow solution of LiTMP. A solution of (2R,6S)-4-[6-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-chloro-3-fluorophenyl]-2,6-dimethylmorpholine (Intermediate 42, 1.1 g, 2.15 mmol) 20 ml THF was cannulated into the LiTMP solution to give a yellow solution which was stirred at −78 for about 1 hour; then N-methoxy-N-methylpyrazine-2-carboxamide (1.077 g, 6.44 mmol) was added. The mixture was stirred at −78° C. After 5 hours the reaction was worked up by adding saturated NH4Cl to the −78° C. solution and extracting with EtOAc (3×). After drying over MgSO4, concentration of the mixture gave material that was purified on SiO2 using 0-10% acetone/hexanes to recover 891 mg (67%) of the title compound as a yellow oil.

1. customto give a yellow solution which
2. stirringThe mixture was stirred at −78° C
3. waitAfter 5 hours the reaction was worked up
4. extractionextracting with EtOAc (3×)
5. dry with materialAfter drying over MgSO4, concentration of the mixture
6. customgave material that
7. customwas purified on SiO2 using 0-10% acetone/hexanes
8. customto recover 891 mg (67%) of the title compound as a yellow oil