N-(3-Bromopropyl)phthalimide

white powder

50mLDMF, 0.025 mol potassium salt of phthalimide, 0.10 mol 1, 3-dibromopropane and 0.5 g TBAB, 70 reaction 2.0h;Cool to room temperature, Pour ice waterEthyl acetate extraction, Washed, dry, De-soluble, Stand overnight, 5.91 g of N- (3-bromopropyl) phthalimide was precipitated as a white solid, m.p. 70-73 ° C, Yield 88.3percent.50 mL DMF, 0.025 mol potassium salt of phthalimide, 0.10 mol 1, 3-dibromopropane and 0.5 g TBAB, reacted at 70°C for 2.0 h; cooled to room temperature, poured into ice water, extracted with ethyl acetate, washed with water , Drying, desolvation, standing overnight, precipitation of a white solid N-(3-bromopropyl) phthalimide 5.91g, mp 70 ~ 73 ° C, the yield of 88.3percent.General 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 HOne g phthalimide potassium (5.4 mmol) was dissolved in 5 mL DMF and then 3 g of 1, 2-dibromoethane 11a (1.4 mL, 16.2 mmol) was added to the mixture and stirred at room temperature.After 23 hours, 30 mL H2O and 10 mL DCM were added to the mixture and then the aqueousphase was separated and extracted with DCM. The organic layer was washed with brine, driedover anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purifiedwith column chromatography on silica gel and eluted with n-hexane and ethyl acetate to give 1-bromo-2-phthalimidoethane 12a as a white solid (0.9 g, 3.54 mmol). Yield: 65.6percentGeneral 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: 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.General procedure: A mixture of dibromoalkane (23 mmol) and potassium carbonate (12 mmol)was added in acetone (30 mL), and potassium phthalimide (10 mmol) was added slowly over a 15-min period, and then the reaction was heated under reflux for 8-10 h. The reaction mixture was filtered, and the acetone was evaporated in vacuo. The crude product was purified by column chromatography on silica gel using mixtures of petroleum/acetone as eluent) to obtain the white solid compounds 2-4. 2-(3-Bromopropyl)-1H-isoindoline-1, 3(2H)-dione (2). Potassium phthalimide was treated with 1, 3-dibromopropane according to the general procedure to give the desired product 2 as white solid, yield 64.7percent, mp: 71.0-72.5 °C.Preparation of Compound 62A: (0449) A solution of 1, 3-dibromopropane (16.4 g, 81.0 mmol) and potassium phthalimide (5.0 g, 27.0 mmol) in DMF (100 mL) was stirred under NTo a stirred solution of isoindoline-1, 3-dione (10 g, 1 mmol)in N, N-dimethyl formamide (DMF) (40 mL), 1, 3-dibromopropane (14 g, 1 mmol), K2CO3 (9.3 g, 3 mmol) were addedat room temperature. The reaction mixture was stirred atroom temperature for 3 h. After completion of the reaction, as indicated by TLC, the resulting solution was poured intoice cold water, which was then extracted with ethyl acetate.Ethyl acetate was separated, dried over Na2SO4 and concentratedunder vacuum to afford a white solid.General procedure: Take 27mmol (4g) of phthalimide in a 250mL flask, add 100mL of anhydrous ethanol, and then heat to reflux until the solid dissolves completely. While hot, the solution in the vial is poured into an ethanol solution containing 0.06mol (3.05g) of KOH. Medium, stirring, suction filtration to give white phthalimide potassium salt.Take 0.45 mol of 1, 3-dibromopropane (1, 4-dibromobutane) in a 250 mL three-neck flask and add 100 mL of dry acetone.0.15 mol (27.7 g) of phthalimide potassium salt was added in batches with stirring, and the mixture was stirred and refluxed for 12 hours.After cooling, the mixture was filtered under suction and the filtrate was evaporated under reduced pressure to remove acetone and excess 1, 3-dibromopropane (1, 4-dibromobutane). The mixture was placed in a freezer overnight and filtered by suction. The solid was collected and recrystallized from absolute ethanol. White crystal Ia (Ib) was obtained.Example 8: Preparation of 2-(3-bromopropylGeneral procedure: To a mixture of dibromoalkane (32.0 mmol), PEG400 (0.23 mL) in acetone (60 mL), compound 2 (2.96 g, 16.0 mmol) was added in portions under refluxing condition. The resulting mixture was heated for 5-8 h. After the reaction was finished, the solvent was evaporated under reduced pressure. Then water (50 mL) was added to the residue and the mixture was extracted with dichloromethane (50 mL×3). The combined organic phases were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The obtained residue was recrystallized from ethanol to afford compound 3-5General 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 K5.0mmol N-(3-hydroxypropyl) phthalimide, 5.00mmol PBrGeneral procedure: To a suspension of the appropriate dibromoalkane (33mmol) and potassium carbonate (18mmol) in anhydrous acetone (30mL), and potassium phthalimide (15mmol) was added slowly over a 15min period, and then the reaction mixture was heated under reflux for 8–10h. The reaction mixture was filtered, and the acetone was evaporated in vacuo. The crude product was purified by column chromatography on silica gel (petroleum/acetone as eluent) to obtain 2a-d as white solid.EXAMPLE 7

Molecular Weight:268.11
XLogP3:2.6
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:266.98949
Monoisotopic Mass:266.98949
Topological Polar Surface Area:37.4
Heavy Atom Count:15
Complexity:256
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes