Réaction #12057

Équation de réaction

trisamine

ammonium acetate

Ethyl isocyanate

DMAP

(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

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

Solvants

DCM

methanol

methanol

water

methanol

DCM

Conditions de réaction

Traitement

1. 1
   AutreThe reaction vessel was sealed
2. 2
   TempératureThe reaction mixture was cooled to room temperature
3. 3
   Autrethe reaction vessel was sealed
4. 4
   Températureheated at 130° C. in a CEM Discoverer™ microwave for 5 min
5. 5
   FiltrationThe reaction mixture was filtered
6. 6
   Lavagethe solid washed with DCM (4 mL) the filtrate
7. 7
   Autrewas evaporated
8. 8
   Autrethe crude product purified by reverse phase preparative HPLC (Prep Nova-Pak HR

Mode opératoire

Ethyl isocyanate (22 mL, 0.31 mmol) was added to a mixture of DMAP (0.008 g, 0.063 mmol) (4R,9aR)-6-hydroxymethyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 15, intermediate b) (0.02 g, 0.063 mmol), 4 Å molecular sieves (0.02 g, crushed) and DCM (2 mL). The reaction vessel was sealed and heated at 140° C. in a CEM Discoverer™ microwave for 15 min. The reaction mixture was cooled to room temperature, DCM (2 mL) and AP-trisamine (2.49 mmol/g, 0.25 g, 0.63 mmol) were added, the reaction vessel was sealed and heated at 130° C. in a CEM Discoverer™ microwave for 5 min. The reaction mixture was filtered and the solid washed with DCM (4 mL) 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 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 (0.053 g, 22% yield) as a pale yellow oil: m/z 391.28 (MH+); HPLC (50% to 80% gradient [95:5 MeOH:water, 10 mmol ammonium acetate] 255 nm XTERRA 2.0 ml/min) 2.98 min, 99%.

Source