Reaktion #606298

Reaktionsgleichung

3-[(R)-1-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-ethyl]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester

2-isopropenyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

Na2CO3

→

3-[(R)-1-((R)-7-isopropenyl-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-ethyl]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester

Ausbeute 92.6%

Lösungsmittel

dioxane

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was cooled to ambient temperature
2. 2
   SonstigeThe solvent was removed in vacuo
3. 3
   Sonstigethe residue was purified by prep-TLC (eluting with 50% EtOAc in petroleum ether)

Vorschrift

A mixture of 3-[(R)-1-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-ethyl]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.128 g, 0.26 mmol), 2-isopropenyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.044 g, 0.259 mmol), Na2CO3 (0.055 g, 0.519 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.042 g, 0.052 mmol) in dioxane (4 mL) and water (1 mL) was stirred at 90° C. for 4 h. The reaction mixture was cooled to ambient temperature. The solvent was removed in vacuo and the residue was purified by prep-TLC (eluting with 50% EtOAc in petroleum ether) to give 3-[(R)-1-((R)-7-isopropenyl-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-ethyl]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.109 g, 59%) as a solid. LC/MS (Table 1, Method 25) Rt=0.925 min.; MS m/z: 455 [M+H]+ and 399 [M+H−56]+. 1H NMR (CDCl3, 400 MHz): δ 8.06 (brs, 1H), 6.79 (s, 1H), 6.65 (s, 1H), 5.25 (s, 1H), 4.86 (s, 1H), 4.70 (q, J=6.8 Hz, 1H), 4.64-4.54 (d, J=13.8 Hz, 2H), 3.96 (d, J=8.0 Hz, 1H), 3.82 (d, J=8.0 Hz, 1H), 3.56 (d, J=8.0 Hz, 1H), 3.42 (d, J=8.0 Hz, 1H), 3.21 (m, 1H), 2.03 (s, 3H), 1.67 (m, 3H), 1.45 (s, 9H), 1.32 (d, J=7.2 Hz, 3H), 1.25 (d, J=15.2 Hz, 3H).

Quelle