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

HRID 1272174

反応式

HRID 1272174 の反応式
C([Li])CCC.[C:6]([O:10][C:11]([N:13]1[CH2:25][C@@H:24]([CH3:26])[N:23]2[C@H:15]([CH2:16][C:17]3[C:22]2=[N:21][C:20](Br)=[CH:19][CH:18]=3)[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].[CH2:28]([S:30]SCC)[CH3:29].C([O-])(=O)C.[NH4+]>O1CCCC1.CO.O>[C:6]([O:10][C:11]([N:13]1[CH2:25][C@@H:24]([CH3:26])[N:23]2[C@H:15]([CH2:16][C:17]3[C:22]2=[N:21][C:20]([S:30][CH2:28][CH3:29])=[CH:19][CH:18]=3)[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]

参加物

8

反応物 4

HCID 8077Diethyl disulfideHCID 517165Ammonium AcetateHCID 86590113(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

生成物 1

HCID 69359585(4R,9aR)-6-Ethylsulfanyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester収率 53%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒3 回HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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.

後処理

  1. additionwas added dropwise
  2. temperaturemaintaining the temperature below −70° C
  3. waitThe resultant dark red solution was left
  4. waitThe mixture was left
  5. stirringto stir at −78° C. for 2 h
  6. waitleft
  7. temperatureto warm to room temperature over 2 h
  8. additionthe mixture was poured onto an isolute HM-N SPE cartridge
  9. washeluted with ethyl acetate (10 mL)
  10. customThe eluent was evaporated under reduced pressure
  11. customthe crude material was purified by reverse phase preparative HPLC (Prep Nova-Pak HR

出典と根拠

ORDレコード
ord-2b41990edc55402d81498d97e5c95782
出典データセット
uspto-grants-2007_04
特許番号
US07208494B2

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