Reacción #51541

Ecuación de reacción

2-[(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b)[1,4]thiazepino[6,5,4-hi]indol-6-yl]-5-methoxybenzaldehyde

methyl magnesium bromide

→

title compound

1-{2-[(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indol-6-yl]-5-methoxyphenyl}ethanol

Disolventes

tetrahydrofuran

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.WAITwith warning to ambient temperature for several hours
2. 2
   Otroquenched with sat'd ammonium chloride
3. 3
   ExtracciónExtracted with ethyl acetate
4. 4
   Lavadowashed organics with brine
5. 5
   Secadodried (MgSO4)
6. 6
   Concentraciónconcentrated
7. 7
   OtroThe residue was purified by prep HPLC (
8. 8
   LavadoC18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA)
9. 9
   workup.ADDITIONFractions containing desired compound
10. 10
    Extracciónextracted with ethyl acetate
11. 11
    Secadodried (MgSO4)
12. 12
    Concentraciónconcentrated

Procedimiento

To a solution of 2-[(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b)[1,4]thiazepino[6,5,4-hi]indol-6-yl]-5-methoxybenzaldehyde, the free base of EXAMPLE 16 (0.03 g, 0.08 mmol), in 5 mL of tetrahydrofuran at 0° C. was added methyl magnesium bromide (0.52 mL of a 3M solution in THF, 1.58 mmol). Stirred with warning to ambient temperature for several hours and then quenched with sat'd ammonium chloride. Extracted with ethyl acetate, washed organics with brine, dried (MgSO4) and concentrated. The residue was purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA). Fractions containing desired compound were then immediately free based with 1 N sodium hydroxide, extracted with ethyl acetate, dried (MgSO4) and concentrated to afford the title compound of EXAMPLE 21. LRMS (ES+): 397.1 (M+H)+.

Fuente