N-(5-BROMOPENTYL)PHTHALIMIDE

General procedure: The appropriate dibromoalkane derivative 2a-2e (11.9 mmol) was added slowly to a mixture of the starting material phthalimide potassium salt (1) (1g, 5.4 mmol) and anhydrous KGeneral procedure: A mixture of phthalimide10(6.8 mmol) dissolved in EtOH (20 mL) was gently boiled for about 1h. The hot solution was decanted from any solid into 1.25 mL of a specially prepared solution of KOH (15.25 g KOH dissolved in 15 mL of HGeneral procedure: Acetone (150mL) and dibromoalkyl (30mol) were added to a 250mL three-necked round-bottom flask fitted with a mechanical stirrer and reflux condenser. Potassium phthalimide (11.85g, 10 mol) was added slowly over a 15-min period, and then the reaction mixture was heated under reflux for 10h. The reaction mixture was filtered via suction, and the acetone was removed via rotary evaporation. The crude product was purified by flash chromatography on silica gel (EtOAc:petroleum ether=1:14) to afford 2–5 as white solid.To a stirred solution of 1, 5-dibromopentane (13-k) (170.58 mL, 1.26 mol) in DMF (1.5 L) was added potassium phthalate (12-k) (78.0 g, 0.42 mol) portion-wise over 30 mm at room temperature. After complete addition, the reaction mixture was stirred at 90°C for 1 8 h, then quenched with water (3 L) and extracted with diethyl ether (500 mL x 4). The combined organic extracts were washed with water (500 mL x 2), followed by brine (500 mL x 2) and dried over anhydrous sodium sulfate, filtered anad concentrated under reduced pressure to obtain the crude. The residue was purified by silica gel column chromatography (60-120 mesh) using 5-10percent EtOAc / hexanes to afford 14-k as an off-white solid (81 g, 65percent yield).H NMR (400 MHz, CDCI3): d 7.82 (dd, J= 5.5, 3.1 Hz, 2H), 7.69 (dd, J= 5.5, 3.0 Hz, 2H), 3.68 (t, J= 7.2 Hz, 2H), 3..38 (t, J= 6.8 i-iz, 2Ff). 1.93-1.85 (n:i, 2H), 1.70 (p, J= 7, 5 Hz, 2H), 1.53-1.43 (m, 2H).o a stirred solution of 1, 5-dibromopentane (13-k) (170.58 mL, 1.26 mol) in DMF (1.5 L) was added potassium phthalate (12-k) (78.0 g, 0.42 mol) portion-wise over 30 min at room temperature. After complete addition, the reaction mixture was stirred at 90°C for 18 h, then quenched with water (3 L) and extracted with diethyl ether (500 mL x 4). The combined organic extracts were washed with water (500 mL x 2), followed by brine (500 mL x 2) and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude. The residue was purified by silica gel column chromatography (60-120 mesh) using 5-10percent EtOAc / hexanes to afford 14-k as an off-white solid (81 g, 65percent yield).1H NMR (400 MHz, CDC1To a stirred solution of 1, 5-dibromopentane (13-k) (170.58 mL, 1.26 mol) in DMF (1.5 L) was added potassium phthalate (12-k) (78.0 g, 0.42 mol) portion-wise over 30 mm at room temperature. After complete addition, the reaction mixture was stirred at 90°C for 18 h, then quenched with water (3 L) and extracted with diethyl ether (500 mL x 4). The combined organic extracts were washed with water (500 mL x 2), followed by brine (500 mL x 2) and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude. The residue was purified by silica gel column chromatography (60-120 mesh) using 5-10percent EtOAc / hexanes to afford 14-k as an off-white solid (81 g, 65percent yield). ‘HNMR (400 IVIFIz, CDC13): 7.82 (dd, J= 5.5, 3.1 Hz, 2H), 7.69 (dd, J 5.5, 3.0 Hz, 2H), 3.68 (t, J 7.2 Hz, 2H), 3.38 (t, J 6.8 Hz, 2H), 1.93-1.85 (m, 2H), 1.70 (p, J= 7.5 Hz, 2H), 1.53-1.43 (m, 2H).To a stirred solution of 1, 5-dibromopentane (13-k) (170.58 mL, 1.26 mol) in DMF (1.5 L) was added potassium phthalate (12-k) (78.0 g, 0.42 mol) portion-wise over 30 min at room temperature. After complete addition, the reaction mixture was stirred at 90°C for 18 h, then quenched with water (3 L) and extracted with diethyl ether (500 mL x 4). The combined organic extracts were washed with water (500 mL x 2), followed by brine (500 mL x 2) and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude. The residue was purified by silica gel column chromatography (60-120 mesh) using 5-10percent EtOAc / hexanes to afford 14-k as an off-white solid (81 g, 65percent yield). 1H NMR (400 MHz, CDC13): δ 7.82 (dd, J= 5.5, 3.1 Hz, 2H), 7.69 (dd, J= 5.5, 3.0 Hz, 2H), 3.68 (t, J= 7.2 Hz, 2H), 3.38 (t, J= 6.8 Hz, 2H), 1.93-1.85 (m, 2H), 1.70 (p, J= 7.5 Hz, 2H), 1.53-1.43 (m, 2H).To a stirred solution of 1, 5-dibromopentane (13-k) (170.58 mL, 1.26 mol) in DMF (1.5 L) was added potassium phthalate (12-k) (78.0 g, 0.42 mol) portion-wise over 30 mm at room temperature. After complete addition, the reaction mixture was stirred at 90°C for 18 h, then quenched with water (3 L) and extracted with diethyl ether (500 mL x 4). The combined organic extracts were washed with water (500 mL x 2), followed by brine (500 mL x 2) and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude. The residue was purified by silica gel column chromatography (60-120 mesh) using 5-10percent EtOAc / hexanes to afford 14-k as an off-white solid (81 g, 65percent yield).‘H NMR (400 MHz, CDC13): 7.82 (dd, J= 5.5, 3.1 Hz, 2H), 7.69 (dd, J= 5.5, 3.0 Hz, 2H), 3.68 (t, J 7.2 Hz, 2H), 3.38 (t, J 6.8 Hz, 2H), 1.93-1.85 (m, 2H), 1.70 (p, J= 7.5 Hz, 2H), 1.53-1.43 (m, 2H).[0714] Step 11: Synthesis of 2-(5-bromopentyl) isoindoline-1, 3-dione (14-k) To a stirred solution of 1, 5-dibromopentane (13-k) (170.58 mL, 1.26 mol) in DMF (1.5 L) was added potassium phthalate (12-k) (78.0 g, 0.42 mol) portion-wise over 30 min at room temperature. After complete addition, the reaction mixture was stirred at 90°C for 18 h, then quenched with water (3 L) and extracted with diethyl ether (500 mL x 4). The combined organic extracts were washed with water (500 mL x 2), followed by brine (500 mL x 2) and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude. The residue was purified by silica gel column chromatography (60-120 mesh) using 5-10percent EtOAc / hexanes to afford 14-k as an off-white solid (81 g, 65percent yield). [65] To a solution of 1, 5-dibromopentane (9.00 ml, 65.22 mmol) dissolved in DMF (100 ml) was added potassium phthalimide (12.08 g, 65.22 mmol) at room temperature, and the reaction mixture was stirred for 24 hours. After the reaction was completed, distilled water was added, and the resulting reaction mixture was stirred for 10 minutes and extracted with ethyl acetate three times. Then, the organic phase was washed with a saline solution, dried with anhydrous magnesium sulfate and distilled under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluent: ethyl acetate:hexane = 1:3) to give the target compound (10.6 g, 55 percent).[66] 8.7ml (6 · 5 X 10General procedure: Compound 6–9 was prepared according the literature reported by Cheng L etal. [34] and with some modifications. Namely, phthalimide (2.9g, 20mmol) and the appropriate dibromoalkanes (80mmol) were added into MeCN (50mL). After an addition of KA solution of 5-phthalimido-1-pentanol (0.53 g, 2.3 mmol) andtriphenylphosphine (0.66 g, 2.5 mmol) in dichloromethane(25 mL) was cooled to 0 C. N-Bromosuccinimide (0.45 g, 2.5 mmol) was added portion-wise over 10 min and stirring wascontinued at 0 C for 3 h. The reaction mixture diluted with dichloromethane(9 mL) and extracted with water (3 15 mL) and brine(15 mL). The organics were dried over sodium sulfate and concentratedunder reduced pressure. The residue was purified on silicagel (30percent ethyl acetate/hexane) to yield the product as a clear colorlessoil (0.54 g, 1.82 mmol, 80percent). 1H NMR (500 MHz, CDCl3) d 7.82(m, 2H), 7.71 (m, 2H), 3.68 (t, 2H, J = 7.5 Hz), 3.38 (t, 2H, J = 7 Hz), 1.88 (m, 2H), 1.69 (m, 2H), 1.46 (m, 2H); 13C NMR (125 MHz, CDCl3) d 168.31, 133.86, 132.01, 123.13, 37.56, 33.34, 32.11, 27.65, 25.31Then, 16.2 g of 5-phthalimido-1-pentanol was dissolved in 350 ml of diethyl ether, and 4.3 ml of phosphorus tribromide was added dropwise at 0° C.

Molecular Weight:296.16
XLogP3:3.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:5
Exact Mass:295.02079
Monoisotopic Mass:295.02079
Topological Polar Surface Area:37.4
Heavy Atom Count:17
Complexity:282
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes