Reaktion #12053

Reaktionsgleichung

ethyl disulfide

ammonium acetate

n-Butyl lithium

(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

(4R,9aR)-6-(2-hydroxy-ethoxymethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

intermediate b

(4R,9aR)-6-(2-hydroxy-ethoxymethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

→

title compound

Ausbeute 53.0%

(4R,9aR)-6-Ethylsulfanyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

Ausbeute 53.0%

Lösungsmittel

methanol

methanol

water

methanol

THF

THF

Water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   Temperaturmaintaining the temperature below −70° C
3. 3
   workup.STIRRINGThe resultant dark red solution was stirred at −78° C. for 30 min
4. 4
   workup.STIRRINGThe mixture was stirred at −78° C. for 2 h
5. 5
   workup.WAITleft
6. 6
   Temperaturto warm to room temperature over 2 h
7. 7
   workup.ADDITIONthe mixture was poured onto an isolute HM-N SPE cartridge
8. 8
   Wascheneluted with ethyl acetate (10 mL)
9. 9
   SonstigeThe eluant was evaporated under reduced pressure
10. 10
    Sonstigethe crude material was purified by reverse phase preparative HPLC (Prep Nova-Pak HR

Vorschrift

THF (5 mL) was cooled to −78° C. under an argon atmosphere. n-Butyl lithium (1.6 M in hexanes, 0.5 mL, 0.8 mmol) was added and the mixture was stirred at −78° C. for 5 min. A mixture of (4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 5, intermediate b) (0.2 g, 0.54 mmol) in THF (5 mL) was added dropwise, maintaining the temperature below −70° C. The resultant dark red solution was stirred at −78° C. for 30 min and ethyl disulfide (0.13 mL, 1.08 mmol) was added. The mixture was stirred at −78° C. for 2 h and left to warm to room temperature over 2 h. Water (1 mL) was added and the mixture was poured onto an isolute HM-N SPE cartridge and eluted with ethyl acetate (10 mL). The eluant was evaporated under reduced pressure and the crude material was purified by reverse phase preparative HPLC (Prep Nova-Pak HR C18 6 μm 60 Å 30 mm×300 mm column, UV detection at 254 nm, mobile phase 95:5 methanol:water and 10 mmol ammonium acetate, gradient 50 methanol to 100% 0 to 10 min then 100% methanol to 13 min, 20 mL/min) to afford the title compound (0.071 g, 53% yield) as a pale yellow oil: m/z 350.14 (MH+); HPLC (50% to 80% gradient [95:5 MeOH:water, 10 mmol ammonium acetate] 220 nm XTERRA 2.0 ml/min) 6.21 min. (4R,9aR)-6-Ethylsulfanyl-4-methyl-1,2,3,4,9,9a-hexahydro-2-4a,5-triaza-fluorene

Quelle