C[Mg+].[Br-].[C:4]1(C)C=CC=CC=1.C1COCC1.[C:16]([C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][N:21]=1)([CH3:19])([CH3:18])[CH3:17].[BH4-].[Na+]>C1COCC1.C(Cl)Cl.O.CO>[C:16]([C:20]1[N:21]=[CH:22][C:23]([CH:24]([NH2:25])[CH3:4])=[CH:26][CH:27]=1)([CH3:19])([CH3:17])[CH3:18]A solution of MeMgBr 1.4 M 75/25 toluene/THF (8.9 ml, 12.48 mmol) is added dropwise over 5 min to an ice cooled solution of 6-tert-butylnicotinonitrile (intermediate 21) (1 g, 6.24 mmol) in 15 mL of THF. The reaction is stirred for 6 hr and cooled with a dry ice bath. MeOH is then added dropwise followed by the incremental addition of NaBH4 (0.59 g, 15.9 mmol). The reaction is stirred over night, water and CH2Cl2 are then added and the resulting paste is filtered through celite and rinsed with CH2Cl2. The reaction is concentrated to remove the organics and extracted 3 times with ethyl acetate. The combined organic layers are extracted with 1 H HCl. The aqueous layer is basified with 28% NH4OH and extracted 3 times with ethyl acetate. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated. (Yield: 488 mg, 49%). 1H NMR (400 MHz, CDCl3) δ ppm 1.36 (s, 9 H) 1.40 (d, J=6.60 Hz, 3 H) 4.15 (q, J=6.60 Hz, 1H) 7.31 (d, J=8.20 Hz, 1 H) 7.63 (dd, J=8.20, 2.34 Hz, 1 H) 8.52 (d, J=2.34 Hz, 1 H).
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