(3-BROMOPROPOXY)-TERT-BUTYLDIMETHYLSILANE

3-(3-(2, 5-Dioxo-4-(3, 4, 5-trimethoxyphenyl)-2, 5-dihydro-1H-pyrrol-3-yl)-1H-indol-1-yl)propyl 2-amino-4-methylpentanoate 3-Bromopropoxy-tert.-butyldimethylsilan A modified procedure of Galka et al. (J. Lab. Comp. Rad. 2005, 48(11): 797-809) was used to prepare the title compound. A mixture of 3-bromopropanol (39.1 mmole; 5.43 g), tert.-butyldimethylsilylchloride (43.2 mmole; 6.47 g) and imidazole (46.7 mmole; 3.20 g) was stirred at RT for 3 hours under inert gas. The reaction was quenched with water, extracted with diethylether, the organic layer dried over MgSO3-Bromopropoxy-ferf.-butyldimethylsilanA modified procedure of Galka et al. (J. Lab. Comp. Rad. 2005, 48(11): 797-809) was used to prepare the title compound. A mixture of 3-bromopropanol (39.1 mmole; 5.43 g), te/t-butyldimethylsilylchloride (43.2 mmole; 6.47 g) and imidazole (46.7 mmole; 3.20 g) was stirred at RT for 3 hours under inert gas. The reaction was quenched with water, ex- tracted with diethylether, the organic layer dried over MgS0fresh 3-bromo-1-propanol (2 ml, 22.12 mmol) was dissolved in dry CH2Cl2 (8 ml). Triethylamine (3.39 ml, 24.33 mmol) and 4-(dimethylamino)pyridine (0.29 g, 2.433 mmol) were added under argon with stirring. The solution was cooled to 0 °C under argon, and t-butyldimethylsilyl chloride (3.33 g, 22.12 mmol) was added. The solution was allowed to come to room temperature while stirring for 3 h under argon (monitored by TLC using 15percent ethyl acetate/hexane with anisaldehyde detection). The reaction was quenched with water (5 ml) and allowed to stir for 15 min. The crude product was extracted from the aqueous solution with CH2Cl2, (3 * 10 ml). The combined organic extracts were dried over Na2SO4, filtered, and evaporated. Crude (3-bromopropoxy)-t-butyldimethylsilyl ether was purified on a silica gel column using 15percent ethyl acetate/hexane to yield 4.52 g, 17.85 mmol, 81percent yield, as a yellow oil. 1H NMR (CDCl3) d (ppm): 0.089 (s, 3H, SiCH3); 0.094 (s, 3H, SiCH3); 0.91 (s, 9H, t-Bu); 2.06 (m, 2H, BrCH2CH2CH2O); 3.53 (t, J = 5.7Hz, 2H, BrCH2CH2CH2O); 3.75 (t, J = 5.7 Hz, 2H, BrCH2CH2CH2O).To lH-imidazole (13.4 g, 197 mmol) in DCM (100 mL) was added 3-bromopropan-l-ol (13.7 g, 99 mmol) followed slowly by fe/ butylchlorodimethylsilane (17.8 g, 118 mmol) in DCM (20 ml). After 3 hr at RT, the reaction was concentrated to ~100 mL and poured in EtOAc (800 mL), washed with 5percent aq citric acid (2 x 200 mL) and brine. The organic layer was dried over MgSCM, filtered and concentrated to yield the title compound (10.0 g, 39.5 mmol, 40 percent yield). *H NMR (400 MHz, chloroform-tf) δ ppm 3.78 (t, 7=5.70 Hz, 2 H), 3.56 (t, 7=6.46 Hz, 2 H), 2.07 (t, 7=5.83 Hz, 2 H), 0.94 (s, 9 H), 0.11 (s, 6 H).Into a 500 ml round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed N, N-dimethylformamide (300 ml), 3-bromopropan-1-ol (30 g, 215.84 mmol, 1.21 equiv.), tert-butyl(chloro)dimethylsilane (26.8 g, 177.81 mmol, 1.00 equiv.), 4H- imidazole (36.4 g, 534.69 mmol, 3.01 equiv.). The resulting solution was stirred for 12 h at25 °C. The resulting solution was diluted with 500 ml of ethyl acetate. The resulting mixture was washed with 3x500 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate. This resulted in 12.4 g of the title compound as colorless oil (28percent). ‘H NMR (300 MHz, CDC13) & 3.76-3.73 (m, 2H), 3.67-3.62 (m, 1H), 3.51 (t, 1=6.6Hz, 1H), 2.07-1.9 1 (m, 2H), 0.87 (s, 9H), 0.07 (s, 6H).3-Bromopropanol (4.14 g, 30 mmol), Was added to DCM (50 mL), imidazole (2.5 g, 30 mmol) was added, stirred under ice for 10 min, TBDMS (4.5 g, 30 mmol) was added and the reaction was continued at room temperature. The next day, DCM (50 mL) (30 mL X3), dried over anhydrous magnesium sulfate and concentrated to give 7 g of a colorless oil in 92percent yield

The propanol functionality of this versatile reagent can be introduced to many pharmaceuticals.1,2,3,4

Molecular Weight:253.25
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:5
Exact Mass:252.05450
Monoisotopic Mass:252.05450
Topological Polar Surface Area:9.2
Heavy Atom Count:12
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes