C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl[C:32]1[CH:37]=[CH:36][C:35]([CH:38]2[CH2:42][C:41](=[O:43])[C:40]([CH3:45])([CH3:44])[CH2:39]2)=[C:34]([F:46])[CH:33]=1.[CH3:47][N:48]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N>[CH3:44][C:40]1([CH3:45])[C:41](=[O:43])[CH2:42][CH:38]([C:35]2[CH:36]=[CH:37][C:32]([C:47]#[N:48])=[CH:33][C:34]=2[F:46])[CH2:39]1Di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (1.75 g, 4.11 mmol) is added to a solution of 4-(4-chloro-2-fluoro-phenyl)-2,2-dimethyl-cyclopentanone (33 g, 137.10 mmol), zinc cyanide (9.66 g, 82.26 mmol), and N-methylpyrrolidone (148.50 mL) at 125° C. and the mixture is stirred for 15 minutes. π-Allylpalladium(II) chloride dimer (0.76 g, 4.11 mmol) is added to the solution and the mixture is stirred for 30 minutes. Diatomaceous earth (15 g) is added and the mixture is cooled to rt. The mixture is filtered through diatomaceous earth and washed with MTBE (450 mL). Water (450 mL) is added and the mixture is extracted with MTBE (150 mL). The mixture is washed with brine, dried over MgSO4, filtered, and concentrated to dryness to give the title compound (34 g, 97%). 1H NMR (300.16 MHz, CDCl3) δ 7.47-7.33 (m, 3H), 3.76-3.63 (m, 1H), 2.83-2.76 (m, 1H), 2.43-2.33 (m, 1H), 2.25 (dd, J=6.3, 12.6 Hz, 1H), 1.91 (t, J=12.3 Hz, 1H), 1.168 (s, 3H), 1.147 (s, 3H).
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