반응 #51541

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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

용매

tetrahydrofuran

THF

반응 조건

후처리

1. 1
   workup.WAITwith warning to ambient temperature for several hours
2. 2
   기타quenched with sat'd ammonium chloride
3. 3
   추출Extracted with ethyl acetate
4. 4
   세척washed organics with brine
5. 5
   건조dried (MgSO4)
6. 6
   농축concentrated
7. 7
   기타The residue was purified by prep HPLC (
8. 8
   세척C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA)
9. 9
   workup.ADDITIONFractions containing desired compound
10. 10
    추출extracted with ethyl acetate
11. 11
    건조dried (MgSO4)
12. 12
    농축concentrated

실험 절차

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)+.

출처