Dichloromethane → (4R,9aR)-4-Methyl-6-(pyrrolidine-1-carbonyloxymethyl)-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 11962

Reaktionsgleichung

Reaktionsgleichung von HRID 11962
[C:1]([O:5][C:6]([N:8]1[CH2:20][CH:19]([CH3:21])[N:18]2[CH:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH2:22][OH:23])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.[C:27](C1NC=CN=1)(C1NC=CN=1)=[O:28].[NH:39]1[CH2:43][CH2:42][CH2:41][CH2:40]1>CO.O>[C:22]([O-:23])(=[O:28])[CH3:15].[NH4+:8].[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH2:22][O:23][C:27]([N:39]2[CH2:43][CH2:42][CH2:41][CH2:40]2)=[O:28])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Komponenten

8

Edukt 4

HCID 6344Dichloromethane2×HCID 31268PyrrolidineHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 695568696-hydroxymethyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

Produkt 2

HCID 517165Ammonium AcetateHCID 69557047(4R,9aR)-4-Methyl-6-(pyrrolidine-1-carbonyloxymethyl)-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittel3×HCID 962WaterLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of 6-hydroxymethyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (0.02 g, 0.063 mmol) and DCM (1 mL) was cooled to 0° C. and carbonyl diimidazole (0.010 g, 0.063 mmol) was added, the mixture was stirred at 0° C. for 2 h and stirred at room temperature for 3 h. A mixture of pyrrolidine (10 mL, 0.13 mmol) and DCM (1 mL) was added and the reaction mixture was sealed and shaken at 60° C. for 48 h. The reaction mixture was cooled and water (2 mL) added, the mixture was shaken at room temperature for 1 h then filtered through a PTFE frit. The filtrate was evaporated and the crude product 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) to afford the title compound (0.16 g, 61% yield) as a pale yellow oil: m/z 417.07 (MH+); HPLC (50% to 80% gradient [95:5 MeOH:water, 10 mmol ammonium acetate] 255 nm XTERRA 2.0 ml/min) 4.20 min, 99.3%.

Aufarbeitung

  1. stirringstirred at room temperature for 3 h
  2. additionwas added
  3. customthe reaction mixture was sealed
  4. stirringshaken at 60° C. for 48 h
  5. temperatureThe reaction mixture was cooled
  6. stirringthe mixture was shaken at room temperature for 1 h
  7. filtrationthen filtered through a PTFE frit
  8. customThe filtrate was evaporated
  9. customthe crude product purified by reverse phase preparative HPLC (Prep Nova-Pak HR

Quellen und Nachweise

ORD-Eintrag
ord-fff4071b81fb4b7f95c5b75670c0f940
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07098337B2

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