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CAS No. : | 627-18-9 | MDL No. : | MFCD00002942 |
Formula : | C3H7BrO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | RQFUZUMFPRMVDX-UHFFFAOYSA-N |
M.W : | 138.99 | Pubchem ID : | 12308 |
Synonyms : |
|
Num. heavy atoms : | 5 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 1.0 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 25.57 |
TPSA : | 20.23 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.68 cm/s |
Log Po/w (iLOGP) : | 1.5 |
Log Po/w (XLOGP3) : | 0.66 |
Log Po/w (WLOGP) : | 0.76 |
Log Po/w (MLOGP) : | 0.96 |
Log Po/w (SILICOS-IT) : | 0.78 |
Consensus Log Po/w : | 0.93 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 3.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.99 |
Solubility : | 14.4 mg/ml ; 0.103 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.66 |
Solubility : | 30.3 mg/ml ; 0.218 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.34 |
Solubility : | 6.31 mg/ml ; 0.0454 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.14 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P264-P270-P280-P301+P312-P305+P351+P338-P310-P330-P501 | UN#: | 1760 |
Hazard Statements: | H302-H318 | Packing Group: | Ⅲ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In tetrahydrofuran at 0 - 20℃; for 15 h; | Potassium carbonate (269 g) and pyrrolidine (200 mL) were added in that order to a THF solution (500 mL) of 3-bromopropanol (200 g) at 0°C. The reaction liquid was stirred at room temperature for 15 hours, then ethyl acetate (500 mL) was added to it, and further stirred at room temperature for 1 hour. The obtained reaction liquid was filtered through Celite, and the solid on the Celite was washed with ethyl acetate. The wash liquid and the filtrate were concentrated under reduced pressure, and ethyl acetate (500 mL) was added to the resulting residue, then stirred for 1 hour and filtered through Celite. The filtrate was concentrated under reduced pressure, and the resulting residue was purified through distillation (boiling point: 62°C, 1 mmHg) to obtain (3-hydroxypropyl)pyrrolidine (156 g, yield 95 percent). 1HNMR (400 MHz, CDCl3, δ ppm): 1.69-1.78 (6H, m), 2.53-2.59 (4H, m), 2.73 (2H, t, J=5.6 Hz), 3.81 1 (2H, t, J=5.4 Hz), 5.58 (1H, brs) |
86.3% | Stage #1: at 80℃; for 5.5 h; Stage #2: With potassium carbonate In dichloromethane; water |
To a solution of pyrrolidine (1.5 g, 19.5 mmol) in toluene (10 rnL) was added 3- bromopropanol (5.4 g, 39.0 mmol) and and the reaction mixture heated at 8O0C for 5.5 hrs. After cooling to RT, the toluene was evaporated at reduced pressure and the residue partitioned between DCM (25 mL) and aqueous K2CO3 (25 mL). The organic layer was collected and the aqueous phase extracted with DCM (4 x 25 mL). The combined organic layers were evaporated at reduced pressure to provide the title compound (1.2 g, 86.3 percent) as brown oil.1H NMR (500 MHz, MeOD) δ ppm 3.61 (2 H, t, J=6.3 Hz), 2.48 - 2.71 (6 H, m), 1.70 - 1.89 (6 H, m). |
70% | With potassium carbonate In tetrahydrofuran at 0 - 20℃; for 15 h; | Potassium carbonate (1.4 g, 0.94 mol) and pyrrolidine(0.87 mL, 1.8 mol) were added to a stirred solution of 3-bromopropanol (1 g, 0.635 mol) in30 mL of THF at 0 °C, and the resulting mixture was stirred at room temperature for 15 h.The resulting mixture was diluted with ethyl acetate (200 mL) and filtered through celite.The filtrate was concentrated, and the residue was subjected to column chromatography(silica gel), eluting with 50percent methanol in dichloromethane, to yield a yellow oil (0.57 g,70percent). 1HNMR (300 MHz, CDC13) 3.79 (t, J = 5.1 Hz, 2 H), 2.71 (t, J= 5.6 Hz, 2 H), 2.57-2.51 (m, 4 H), 1.75-1.66 (m, 6 H); ‘3C NMR (125 MHz, CDC13) 64.18, 56.02, 54.09,29.24, 23.27. |
69% | With potassium carbonate In tetrahydrofuran at 0 - 20℃; | Preparation of Compound 48,53-(pyrrolidin-1-yl)propan-1-ol [0068] Pyrrolidine (1 .00 ml_, 12.0 mmol) was added to a suspension of potassium carbonate (1 .29 g, 9.35 mmol) and 3-bromopropanol (0.65 ml_, 7.2 mmol) in dry THF (3 mL) at 0 °C. The reaction mixture was then allowed to warm to rt, stirred overnight, diluted with EtOAc, filtered through a silica pad and the filtrate concentrated to afford the title compound (645 mg, 69percent) as a colourless oil.1H NMR (500 MHz, CDCl3) δ 5.54 (br s, 1 H), 3.84 - 3.77 (m, 2H), 2.77 - 2.68 (m, 2H), 2.60 - 2.53 (m, 4H), 1 .80 - 1 .68 (m, 6H). LRMS (ESI+) (M + H)+: 130.12 |
59% | at 20℃; for 48 h; | 3-Bromopropan-1-ol (27.3mL, 302mmol) was added to a solution of pyrrolidine (47.2g, 655mmol) in toluene (1000mL) and the mixture was stirred at room temperature for 48 hours. The reaction mixture was then filtered and the filtrate was evaporated under reduced pressure. The residue was distilled and the title product was obtained as a colourless liquid at 100°C/7mmHg, (23.1g, 59percent). 1H-NMR(CDCl3, 400MHz) δ: 1.60-1.82(m, 6H), 2.50-2.60(m, 4H), 2.75(m, 2H), 3.80(m, 2H) MS ES+ m/z 130 [MH]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate In toluene at 75 - 80℃; for 8 h; | To the reaction bottle were added 913.5 g of toluene, 174 g of morpholine and 556 g of 3-bromopropanol, and 331.2 g of potassium carbonate was added under stirring,The reaction was heated at 75-80 ° C for 8 hours. After completion of the reaction, pressure filtration and concentration of the filtrate to remove toluene and unreacted raw materials, obtained light yellow278.4 g of N - (3-hydroxypropyl) morphorphine, a molar yield of 96percentGas purity was 98.5percent. |
88.5% | at 80℃; for 4 h; | Morpholine 2a(3.1g, 36mmol) and 3-bromo-1-propanol (2.5g, 18mmol) were dissolved in 20mL of toluene at 80° C for 4 hours. The reaction was cooled to room temperature and the reaction was filtered. The filter cake was washed with ethyl acetate (2 mL X 2) and concentrated under reduced pressureThe filtrate gave the title product 3-morpholinopropan-1-ol 2b (2.3 g, yellow oil), yield: 88.5percent. |
50% | at 50℃; for 18 h; | To a mixture of morpholine (33 mL, 371 mmol) and CH2C12(650 mL) was added 3-bromopropanol (25.8 g, 186 mmol), andthe mixture was heated at 50 °C for 18 h. The reaction wascooled, diluted with CH2C12/ and filtered. The filtrate waschromatographed (150 g SiC>2,; CH2C12 to 5percent 2 M NH3/MeOH inCH2C12) to give the title compound as a liquid (27.0 g,50percent) ..NMR (250 MHz, DMSO-dg) : 8 1.50(m, 2H) , 2.24(m, 6H), 3.36(t,J= 6.5 Hz, 1H) , 3.49(111, 2H) , 4.36(s, 1H) .FIA-MS, m/e: 146.1 (m+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | at 80℃; | Intermediate 7: 3-(4-Methylpiperazin-1-yl)-propan-1-ol. 1-Methylpiperazine (6.99 mL, 63 mol) was dissolved in toluene (30 mL). 3-Bromo-propanol (2.62 mL, 30 mmol) was added slowly and the mixture was stirred overnight. After heating to 80°C for 2 h and cooling to r.t., the mixture was filtered and the filter cake was washed thoroughly with toluene. After removal of the toluene, the residue was subjected to Kugelrohr distillation (b.p., 180°C / 2 mbar) to obtain a colourless oil (4.08 g, 25.8 mmol, 86 percent). 1H NMR (CDCl3): δ = 1.70 (Ψ-quint, J 5.8 Hz, 2 H), 2.26 (s, 3 H), 2.35-2.6 (m, 8 H), 2.60 (Ψ-t, J = 5.8 Hz, 2 H), 3.77 (Ψ-t, J = 5.3 Hz, 2 H), 4.09 (s, br., 1 H). |
86% | at 20 - 80℃; | Intermediate 9: 3-(4-Methylpiperazin-1-yl)-propan-1-ol. 1-Methylpiperazine (6.99 mL, 63 mol) was dissolved in toluene (30 mL). 3-Bromopropanol (2.62 mL, 30 mmol) was added slowly and the mixture was stirred overnight at r.t.. After heating to 80°C for 2 h and cooling to r.t., the mixture was filtered and the filter cake was thoroughly washed with toluene. After removal of the solvent, the residue was subjected to Kugelrohr distillation (b.p., 180°C / 2 mbar) to obtain a colourless oil (4.08 g, 25.8 mmol, 86 percent). 1H NMR (CDCl3): δ = 1.70 (Ψ-quint, J 5.8 Hz, 2 H), 2.26 (s, 3 H), 2.35-2.6 (m, 8 H), 2.60 (Ψ-t, J = 5.8 Hz, 2 H), 3.77 (Ψ-t, J 5.3 Hz, 2 H), 4.09 (s, br., 1 H). |
86% | at 20 - 80℃; | Intermediate 9: 3-(4-Methylpiperazin-1-yl)-propan-1-ol 1-Methylpiperazine (6.99 mL, 63 mol) was dissolved in toluene (30 mL). 3-Bromopropanol (2.62 mL, 30 mmol) was slowly and the mixture was stirred overnight at r.t. After heating to 80° C. for 2 h and cooling to r.t., the mixture was filtered and the filter cake was thoroughly washed with toluene. After removal of the solvent, the residue was subjected to distillation (b.p., 180° C./2 mbar) to obtain a colourless oil (4.08 g, 25.8 mmol, 86percent). 1H NNR (CDCl3): δ=1.70 (Ψ-quint, J5.8 Hz, 2 H), 2.26 (s, 3 H), 2.35-2.6 (m, 8 H), 2.60 (Ψ-t, J=5.8 Hz, 2 H), 3.77 (Ψ-t, J=5.3 Hz, 2 H), 4.09 (s, br., 1 H). |
86% | at 80℃; | 3-(4-Methylpiperazin-1-yl)-propan-1-ol. 1-Methylpiperazine (6.99 mL, 63 mol) was dissolved in toluene (30 mL). 3-Bromopropanol (2.62 mL, 30 mmol) was added slowly and the mixture was stirred overnight. After heating to 80° C. for 2 h and cooling to r.t., the mixture was filtered and the filter cake was washed thoroughly with toluene. After removal of the toluene, the residue was subjected to Kugelrohr distillation (b.p., 180° C./2 mbar) to obtain a colourless oil (4.08 g, 25.8 mmol, 86percent). 1H NMR (CDCl3): δ=1.70 (Ψ-quint, J5.8 Hz, 2H), 2.26 (s, 3H), 2.35-2.6 (m, 8H), 2.60 (Ψ-t, J=5.8 Hz, 2H), 3.77 (Ψ-t, J=5.3 Hz, 2H), 4.09 (s, br., 1H). |
86% | at 20 - 80℃; | Synthesis of 3-(4-methylpiperazin-1-yl)-propan-1-ol: [Show Image] 1-Methylpiperazine (6.99 mL, 63 mol) was dissolved in toluene (30 mL). 3-Bromopropanol (2.62 mL, 30 mmol) was added slowly and the mixture was stirred overnight at r.t.. After heating to 80°C for 2 h and cooling to r.t., the mixture was filtered and the filter cake was thoroughly washed with toluene. After removal of the solvent, the residue was subjected to Kugelrohr distillation (b.p., 180°C / 2 mbar) to obtain a colourless oil (4.08 g, 25.8 mmol, 86percent). LC/ESI-MS: m/z = 159 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.4% | at 20℃; | This compound has been previously reported in: Pinchuk, A. N. et al. Synthesis and Structure- Activity Relationship Effects on the Tumor Avidity of Radioiodinated Phospholipid Ether Analogues. J. Med. Chem. 49, 2155-2165 (2006). To a stirred solution inside a 125 mL round bottom flask containing 3-bromo-l-propanol (6.95 g, 50 mmol, 1 eq.) in DCM (25 mL) was added 3,4-dihydropyran (5.93 mL, 65 mmol, 1.3 eq.). The mixture was stirred overnight at room temperature at which point TLC showed disappearance of 3-bromo-l-propanol (20percent EtOAc in hexanes, 10 mL, KMn04). The reaction was evaporated and the crude material was purified by flash chromatography on silica gel (20 g silica, 1.5 cm i.d) eluting with 10percent EtOAc: hexanes (100 mL) to obtain the title compound as a clear oil. Yield 86.4percent (9.637 g); TLC (20percent EtOAc in hexanes), Rf - 0.85; 1H NMR (400 MHz, CDC13, δ): 4.59 (t, 1H, J= 3.52 Hz, H7), 3.90-3.81 (m, 2H, H6), 3.55-3.47 (m, 4H, H4 + H5), 2.16-2.08 (m, 2H, H3), 1.90-1.64 (m, 2H, H2), 1.57- 1.50 (m, 4H, HI) ppm ; 13C NMR (100 MHz, CDC13, δ): 98.90 (C7), 64.88 (C6), 62.26 (C5), 32.90 (C3), 30.59 (d, 2J= 6.04 Hz, C4), 25.41 (C2), 19.48 (CI) ppm. |
79% | With pyridinium p-toluenesulfonate In chloroform at 0 - 20℃; for 1.5 h; | To a solution of 3-bromo-1-propanol (2.00 g, 14.39 mmol) in chloroform (20 ml) were added dihydropyran (1.44 ml, 15.83 mmol) and pyridinium p-toluenesulfonate (181 mg, 0.72 mmol) under ice-cooling, and the mixture was stirred at room temperature for 1.5 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with water and saturated brine, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography (hexane:ethyl acetate=20:1) to give the object product as a pale-yellow oil (2.54 g, yield 79percent). 1H NMR(CDCl3 400 MHz) (δ) ppm: 1.50-1.61 (4H, m), 1.67-1.85 (2H, m), 2.10-2.17(2H, m), 3.49-3.57 (4H, m), 3.83-3.91 (2H, m), 4.60-4.63 (1H, m) |
69% | With pyridinium p-toluenesulfonate In dichloromethane at 0 - 20℃; | Intermediate 3 2-(3-bromopropoxy)tetrahydro-2H-pyran To a solution of 3-bromopropan-l -ol (8 g, 57.9 mmol) in DCM(100 mL) was added PPTS (891 mg, 3.6 mmol), then dihydropyran (7.3 g, 86.9 mmol) was added dropwise at 0 °C. The mixture was stirred at room temperature overnight. It was partitioned between DCM and water. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product which was purified by column chromatography eluting with petroleum ether/ethyl acetate (50: 1) to give 2-(3-bromopropoxy)tetrahydro-2H-pyran (8.9 g, 69.0percent yield) as a light yellow oil. |
67% | With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 18 h; Inert atmosphere | In a 300 mL two-neck eggplant type flask, the compound represented by formula (9-3-a) (3-bromo-1-propanol,Molecular weight: 138.99) 6.089 g (43.8 mmol, 1.0 eq.),250 mL of dichloromethane (Super Dehydrated)4.464 g (53.1 mmol, 1.22 eq.) Of dihydropyran (DHP),2.20 g (8.75 mmol, 0.20 eq.) Of pyridinium p-toluenesulfonate was added and the mixture was stirred at room temperature under nitrogen for 18 hours.After stirring was completed, only the desired product was isolated by column chromatography (hexane: ethyl acetate = 9: 1).Thereafter, the solvent was removed by concentration and vacuum drying to obtain a colorless oily compound (2- (3-bromopropoxy) tetrahydro-2H-pyran, molecular weight: 222.11) represented by formula 0 .555 g was obtained. The yield was 6.555 g (25.2 mmol), and the yield was 67percent |
66% | at 20℃; for 5 h; | Into a 250 mL round-bottom flask, was placed 3-bromopropan-1-ol (4.75 g, 34.17 mmol, 1.00 equiv), dichloromethane (100 mL), PPTs (10 mg, 0.04 mmol, 0.10 equiv), 3,4- dihydro-2H-pyran (3.32 g, 39.47 mmol, 1.16 equiv). The resulting solution was stirred for 5 h at room temperature. The mixture was dried over anhydrous magnesium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column eluted with ethyl acetate/petroleum ether (1:5). This resulted in 5 g (66percent) of 2- (3-bromopropoxy)oxane as colorless oil. 1H NMR (300 MHz, CDCl3, 25 oC): 4.62 (t, 1H), 3.95- 3.85 (m, 2H), 3.59-3.48 (m, 4H), 2.18-2.10 (m, 2H), 1.90-1.45 (m, 6H). |
57% | With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; | To a solution of3-bromo-1-propanol (4 g, 28.8 mmol) in DCM (50 mL) was addedTsOH (496 mg, 2.88 mmol) and 3,4-2H-dihydropyran (7.2 g, 86.2 mmol) at 0 °C. The mixturewas stirred at room temperature overnight. The reaction mixture was poured into R~O (100 mL).The mixture was extracted with DCM (70 mL x2). The combined extracts was washed with brine(100 mL), dried over Na2S04 and concentrated to dryness. The residue was purified by silica gelcolumn (PE) to give 2-(3-bromo-propoxy)-tetrahydro-pyran (838 mg, yield: 57percent) as a red solid.[00965] 1H Nl\1R (300 TVIHz, DMSO-d6): 8 = 4.60-4.56 (m, lH), 3.77-3 72 (m, 2H), 3.61-3.56(m, 2H), 3.47-3.42 (m, 2H), 2.07-2.03 (m, 2H), 1. 70-1.61 (m, 2H), 1. 51-1.45 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With potassium carbonate In N,N-dimethyl-formamide | (e) Preparation of N-(3-hydroxypropyl)phthalimide (106). A mixture of 3-bromopropanol (4 g, 0.029 mol), potassium phthalate (8 g, 0.043 mol) and potassium carbonate (4 g, 0.029 mol) in dry DMF (50 ml) was stirred and heated at 70° C. for four hours. The mixture was diluted with water (100 ml) and extracted with ethyl acetate (3*75 ml). The organic extract was washed with water (3*100 ml) and dried (Na2 SO4). Removal of the solvent under reduced pressure left a white solid which was extracted with benzene. The benzene extract was evaporated to a white solid and recrystallized from ethyl acetate-hexanes to give white crystals (1.27 g, 24percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6 g | at 20℃; for 14 h; Cooling with ice | The 3-bromopropanol (10.0 g, 71 . 94 mmol) under cooling in ice dropping slowly added to the methylamine aqueous solution in (50 ml). After the completion of the dropping, the obtained mixture at the room temperature reaction 14 hours. Then obtained directly to the pressure of the concentrated to obtain yellow oily mixture (6.0 g), directly used for the next step reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: With triethylamine In dichloromethane at 20℃; for 0.166667 h; Stage #2: at 0 - 20℃; for 16 h; |
To a stirred solution of 3-hromopropan-.1-oi (8.0 g, 57.55 mmoi) in dry DCM (40 mL), Et3N (12.OmL, 86.32 mmol) was added and stirred at room temperature for 1() mm. After thai Ac20 (6.5 mL, 69.06 mmoi) in DCM (5 mL) was added drop wise 0 °C and stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched with IN HC1 solution and extracted with I)CM. The combined organic layer were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography using 1 0percent EtOAc/hexane to atrd X.10475] Yield: 10.0 g, 96percent; ‘H NMR (400 MHz, CDC13) δ 4.1 9-4.1 7 (m, 2H), 3.47 (t, ./ 6.5 Hz, 2H), 2.21-2.18 (m, 2H), 2.06 (s, 3H). |
96% | With triethylamine In dichloromethane at 0 - 20℃; for 16 h; | To a stirred solution of l-bromo-3-propanol 147 (8.0 g, 57.55 mmol) in dry DCM (40 mL) was added Et3N (12.0 mL, 86.32 mmol) and stirred at room temperature for 10 min. After that acetic anhydride (6.5 mL, 69.06 mmol) in DCM (5 mL) was added dropwise at 0 °C and stirred at room temperature for 16h. Progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched with IN HCl solution and extracted with DCM. Combined organic layer was washed with brine, dried over anhydrous Na2S04 and concentrated under reduced pressure. The crude product was purified by column chromatography using 10percent EtOAc in hexane to afford 148. Yield: 10 g, 96percent; NMR: 1H NMR (400 MHz, Chloroform-d3) δ 4.19 - 4.17 (m, 2H), 3.47 (t, J= 6.5 Hz, 2H), 2.19 (m, 2H), 2.06 (d, J= 3.4 Hz, 3H). |
90% | With triethylamine In dichloromethane at 20℃; | 3-Bromopropanol 4-1 (3.22 g, 23.2 mmol) was mixed with 2.36 g (23.2 mmol) acetic anhydride and 4.73 g (46.6 mmol) of triethylamine in methylene chloride and stirred overnight at room temperature. The resulting solution was washed with 1 M HCl, and the organic layer was removed to afford 3.8 g (90percent) of the product acetate 4-2 as a yellow oil. |
87% | With triethylamine In dichloromethane at 20℃; for 12 h; | 3-Bromopropanol was dissolved in dichloromethane (150 mL) at room temperature, triethylamine (14.5 g, 14.4 mmol) was added successively, Acetic anhydride (14.7 g, 14.4 mmol), followed by reaction at room temperature for 12 hours. The organic phase was adjusted to pH 7 with 0.5 mol / L dilute hydrochloric acid solution (20 mL), the organic phase was separated and the organic phase was saturated with a saturated aqueous solution of sodium bicarbonate (100 mL) Brine solution (100 mL x 1), dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated to dryness to give yellow liquid intermediate 9 (11.4 g, yield 87.percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With hydrogenchloride; dmap; acetic anhydride; sodium hydrogencarbonate In dichloromethane | Preparation 8 3-Bromopropyl acetate Acetic anhydride (74.7 mL, 0.792 mole) was added to a 0°-5° C. solution of 3-bromo-1-propanol (100 g, 0.720 mole) and 4-dimethylaminopyridine (8.79 g, 72.0 mmol) in CH2 Cl2 (500 mL). The reaction was warmed to room temperature for 4 hours and then the reaction was worked up extractively with CH2 Cl2 (200 mL), aqueous 1N HCl (2* 300 mL), saturated NaHCO3 (2* 300 mL) and brine (200 mL) and the solvent was removed in vacuo to give 128.52 g (99percent) of the above titled compound. NMR. MS (FD) m/z=180 (M+, 100percent). Analytical calculated for C5 H9 O2 Br C, 33.17; H, 5.01. Found C, 33.69; H, 5.09. |
99% | With hydrogenchloride; dmap; acetic anhydride In dichloromethane | Preparation 8 3-Bromopropyl acetate Acetic anhydride (74.7 mL, 0.792 mole) was added to a 0°-5°C solution of 3-bromo-1-propanol (100 g, 0.720 mole) and 4-dimethylaminopyridine (8.79 g, 72.0 mmol) in CH2Cl2(500 mL). The reaction was warmed to room temperature for 4 hours and then the reaction was worked up extractively with CH2Cl2(200 mL), aqueous 1N HCl (2X 300 mL), saturated NaHCO3(2X 300 mL) and brine (200 mL) and the solvent was removed in vacuoto give 128.52 g (99percent) of the above titled compound. NMR. MS (FD) m/z= 180 (M+, 100percent). Analytical calculated for C5H9O2Br C, 33.17; H, 5.01. Found C, 33.69; H, 5.09. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | at 20℃; for 3 h; Inert atmosphere | Example C: 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 MgSO4, filtered and concentrated. The purification was achieved by column chromatography (PE) to yield the title compound (36.4 mmole; 93 percent). 1H NMR (300 MHz, CDCl3) 3.73 (t; 3J = 5.7 Hz; 2H; CH2O); 3.51 (t; 3J = 6.4 Hz; 2H; CH2Br); 2.02 (q; 3J = 5.7 Hz; 3J = 6.4 Hz; 2H; CH2CH2CH2); 0.89 (s; 9H; C(CH3)3); 0.06 (s; 6H; 2xCH3). |
93% | at 20℃; for 3 h; Inert atmosphere | 3-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 MgS04, filtered and concentrated. The purification was achieved by column chromatography (PE) to yield the title compound (36.4 mmole; 93 percent). 1 H NMR (300 MHz, CDCI3) 3.73 (t; 3J = 5.7 Hz; 2H; CH20); 3.51 (t; 3J = 6.4 Hz; 2H; CH2Br); 2.02 (q; 3J = 5.7 Hz; 3J = 6.4 Hz; 2H; CH?CH?CH?); 0.89 (s; 9H; C(CH3)3); 0.06 (s; 6H; 2xCH3). |
81% | With dmap; triethylamine In dichloromethane at 0 - 20℃; for 3 h; Inert atmosphere | fresh 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). |
40% | With 1H-imidazole In dichloromethane at 20℃; for 3 h; | 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). |
28% | With 1H-2,2,4-triazole In N,N-dimethyl-formamide at 25℃; for 12 h; Inert atmosphere | 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). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 1H-imidazole In dichloromethane at 20℃; for 0.166667 h; Cooling with ice | 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 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium carbonate In acetonitrile at 95℃; for 4 h; | Intermediate 121: tert-Butyl 4-(3-hvdroxypropyr)piperazine-l -carboxylate A mixture of tert-butyl piperazine-1 -carboxylate (2.75 g, 14.8 mmol), l-bromo-3- propanol (1.43 mL, 16.2 mmol) and potassium carbonate (2.25 mL, 27.5 mmol) in acetonitrile (75 mL) was heated at 950C for 4 hours. The solvent was removed under reduced pressure, and the residue was taken up in dichloromethane (300 mL) and washed with water, brine, EPO <DP n="118"/>dried over sodium sulfate and concentrated under reduced pressure. Chromatography on silica gel with methanol in dichloromethane (0-10percent) gave a tan solid 2.88 g (80percent yield). MS (ESV 245 (MH+) for C12H24N2O3,1H-NMR TCDCl1) δ: 1.44 (m, 9H); 1.70-1.82 (m, 2H); 2.40-2.53 (m, 2H); 2.62-2.65 (m, 2H); 3.43-3.50 (m, 4H); 2.77 (m, 2H); 3.73-3.82 (m, 2H). |
[ 1522-92-5 ]
3-Bromo-2,2-bis(bromomethyl)propanol
Similarity: 0.69
[ 1522-92-5 ]
3-Bromo-2,2-bis(bromomethyl)propanol
Similarity: 0.69
[ 1522-92-5 ]
3-Bromo-2,2-bis(bromomethyl)propanol
Similarity: 0.69