Sodium Carbonate → Phenylmethyl 2-(butylamino)4-((2R)-2-{[[(2S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-(phenyloxy)propyl](phenylmethyl)amino]methyl}-3,4-dihydro-2H-chromen-6-yl)benzoate

Participants

Reaction Conditions

Reaction Steps

Argon gas was bubbled through a solution of (2S)-N-{[(2R)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-chromen-2-yl]methyl}-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-N-(phenylmethyl)-3-(phenyloxy)-1-propanamine (Example 88, 92 mg, 0.14 mmol) in toluene (1.25 mL), tetrahydrofuran (0.25 mL), and aqueous Na2CO3 (0.50 mL of a 2M solution) for 10 minutes. Pd(dppf)Cl2 (10 mg, 0.014 mmol, 0.1 eq.) and phenylmethyl 4-bromo-2-(butylamino)benzoate (Example 193, 52 mg, 0.14 mmol, 1.0 eq.) were added, and argon was bubbled through the mixture for an additional 5 minutes before the mixture was stirred vigorously at 85° C. for 3 hours. The reaction mixture was cooled and filtered through a pad of Celite® with the aid of ethyl acetate. The filtrate was transferred to a separatory funnel where the water layer was removed. The organic layer was dried (MgSO4) and concentrated in vacuo to a crude oil. The crude was purified by flash chromatography on silica gel eluted on a gradient from 100:0 to 90:10 hexanes/ethyl acetate to provide the title compound as a colorless oil (47 mg, 42%): 1H NMR (300 MHz, CDCl3) δ7.95 (d, 1 H)7.69 (t, 1 H), 7.43-7.27 (m, 8 H), 7.23-7.19 (m, 6 H), 6.89 (t, 1 H), 6.84-6.80 (m, 3H), 6.75 (s, 1 H), 6.70 (d, 1 H), 5.29 (s, 2 H), 4.17-4.07 (m, 3 H), 3.83-3.66 (m, 3 H), 3.23 (q, 2 H), 2.93-2.64 (m, 6 H), 2.01-1.96 (m, 1 H), 1.72-1.63 (m, 3 H), 1.50-1.41 (m, 2 H), 0.95 (t, 3 H), 0.84 (s, 9 H), 0.07 (s, 3 H), 0.03 (s, 3 H); MS m/z 799.3 (MH+).

Provenance & Evidence