반응 #1359356

ord-2b41990edc55402d81498d97e5c95782

반응 방정식

CC(=O)[O-].[NH4+]
ammonium acetate
[Li][CH2]CCC
n-butyl lithium
C[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]2Cc3ccc(Br)nc3N21
(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester
CCSSCC
ethyl disulfide
CCSc1ccc2c(n1)N1[C@H](C2)CN(C(=O)OC(C)(C)C)C[C@H]1C
title compound
수율 53.0%
CCSc1ccc2c(n1)N1[C@H](C2)CN(C(=O)OC(C)(C)C)C[C@H]1C
(4R,9aR)-6-Ethylsulfanyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester
수율 53.0%

반응 조건

온도
-78°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    workup.ADDITIONwas added dropwise
  2. 2
    온도maintaining the temperature below −70° C
  3. 3
    workup.WAITThe resultant dark red solution was left
  4. 4
    workup.WAITThe mixture was left
  5. 5
    workup.STIRRINGto stir at −78° C. for 2 h
  6. 6
    workup.WAITleft
  7. 7
    온도to warm to room temperature over 2 h
  8. 8
    workup.ADDITIONthe mixture was poured onto an isolute HM-N SPE cartridge
  9. 9
    세척eluted with ethyl acetate (10 mL)
  10. 10
    기타The eluent was evaporated under reduced pressure
  11. 11
    기타the crude material was purified by reverse phase preparative HPLC (Prep Nova-Pak HR

실험 절차

A solution of n-butyl lithium (1.6 M in hexanes, 0.5 mL, 0.8 mmol) in tetrahydrofuran (5 mL) was stirred at −78° C. for 5 min. under an argon atmosphere. 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 (0.2 g, 0.54 mmol) in tetrahydrofuran (5 mL) was added dropwise, maintaining the temperature below −70° C. The resultant dark red solution was left to stir at −78° C. for 30 min then ethyl disulfide (0.13 mL, 1.08 mmol) was added. The mixture was left to stir at −78° C. for 2 h, then 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 eluent was evaporated under reduced pressure and the crude material was purified by reverse phase preparative HPLC (Prep Nova-Pak HR C18 6 mm 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 give the title compound (0.071 g, 53% yield) as a pale yellow oil: m/z M+ 350.14 (M+1); HPLC (50% to 80% gradient [95:5 MeOH:water, 10 mmol ammonium acetate] 220 nm XTERRA 2.0 mL/min) 6.21 min.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07208494B2uspto-grants-2007_04