Reaktion #51541

Reaktionsgleichung

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

Lösungsmittel

tetrahydrofuran

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITwith warning to ambient temperature for several hours
2. 2
   Sonstigequenched with sat'd ammonium chloride
3. 3
   ExtraktionExtracted with ethyl acetate
4. 4
   Waschenwashed organics with brine
5. 5
   Trocknendried (MgSO4)
6. 6
   Einengenconcentrated
7. 7
   SonstigeThe residue was purified by prep HPLC (
8. 8
   WaschenC18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA)
9. 9
   workup.ADDITIONFractions containing desired compound
10. 10
    Extraktionextracted with ethyl acetate
11. 11
    Trocknendried (MgSO4)
12. 12
    Einengenconcentrated

Vorschrift

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)+.

Quelle