Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[C:3]=1[CH3:14].[C:15]([O:34][CH2:35][C@@H:36]1[NH:40][C:39](=[O:41])[CH2:38][CH2:37]1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:14][C:3]1[C:4]([C:10]([F:13])([F:12])[F:11])=[C:5]([CH:8]=[CH:9][C:2]=1[N:40]1[C@@H:36]([CH2:35][O:34][C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:37][CH2:38][C:39]1=[O:41])[C:6]#[N:7]The bromo-compound 3f (0.5 g, 1.89 mmol) was dissolved in 1,4-dioxane (10 mL) and (R)-5-((trityloxy)methyl)pyrrolidin-2-one (3g) (0.54 g, 1.51 mmol) was added followed by Cs2CO3 (1.2 g, 3.78 mmol) at room temperature. The reaction mixture was degassed with Argon gas for 30 min, Pd2(dba)3 (0.17 g, 0.18 mmol) and Xanthphos (0.21 g, 0.37 mmol) were added and heated to 80° C. for 12 h. After completion of reaction (by TLC), the reaction mixture was diluted with water (20 mL), filtered through celite bed and the filtrate was washed with water (2×20 mL). The organic layer was separated, dried over Na2SO4 and concentrated under reduced pressure to give the crude compound which was purified by column chromatography to afford (R)-3-methyl-4-(2-oxo-5-((trityloxy)methyl)pyrrolidin-1-yl)-2-(trifluoromethyl)benzonitrile (3h) (0.26 g, 26%) as a brown solid.
Wird geladen…