* 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.
Example 3 Synthesis of the Intermediate 3-bromopropyltriphenylphosphonium bromide (Olo-IM3) To a stirred solution of triphenylphosphine (511 g, 1.85 mol; assay: 95.0percent) in toluene (800 g), 1,3-dibromopropane (371 g, 1.82 mol; assay: 99.0percent) was added slowly within 1 hour at <5° C. After complete addition the solution was heated to reflux for 17 hours whereupon a suspension was obtained which was then cooled to room temperature. The product was filtered off at 20° C., washed with toluene (2.x.800 g) and dried under vacuum (21 h, 60° C.) to give 3-bromopropyltriphenylphosphonium bromide (Olo-IM3) as a white, crystalline solid (yield: 757 g, 1.63 mol, 89.6percent).
Reference：
[1] Chemical Communications, 2014, vol. 50, # 45, p. 5993 - 5996
[2] Tetrahedron Letters, 2003, vol. 44, # 24, p. 4547 - 4550
[3] Patent: US2007/232814, 2007, A1, . Location in patent: Page/Page column 24
[4] Tetrahedron Letters, 1985, vol. 26, # 47, p. 5747 - 5748
[5] Tetrahedron, 1981, vol. 37, # 16, p. 2855 - 2860
[6] Journal of the Chemical Society, Dalton Transactions: Inorganic Chemistry (1972-1999), 1984, p. 293 - 296
[7] Tetrahedron, 1973, vol. 29, p. 1169 - 1171
[8] Chemische Berichte, 1894, vol. 27, p. 276
[9] Tetrahedron Letters, 1989, vol. 30, # 37, p. 4953 - 4956
[10] Journal of Organic Chemistry, 2006, vol. 71, # 25, p. 9519 - 9521
[11] European Journal of Organic Chemistry, 2014, vol. 2014, # 1, p. 194 - 197
[12] European Journal of Organic Chemistry, 2016, vol. 2016, # 15, p. 2594 - 2598
[13] Chemistry - A European Journal, 2016, vol. 22, # 42, p. 15144 - 15150
2
[ 51860-45-8 ]
[ 3607-17-8 ]
Yield
Reaction Conditions
Operation in experiment
83%
at 108℃; for 24 h;
(2) Add 100ml three-necked flask with magnetic stirring(3-hydroxypropyl) triphenylphosphonium bromide 2.0 g (5 mmol),Hydrobromic acid (content ≧ 40percent) was added dropwise at 108 ° C until just dissolved,The reaction was refluxed for 24 hours. Cool to room temperature,The solution was slowly added dropwise to 50 times the volume of aqueous solution, a white precipitate precipitation.Vacuum filtration, cold water washing, drying,(3-bromopropyl) triphenylphosphonium bromide (1.9 g, 83percent yield) was obtained as a white solid.
Reference：
[1] Patent: CN107216352, 2017, A, . Location in patent: Paragraph 0062
[2] Organic and Biomolecular Chemistry, 2006, vol. 4, # 23, p. 4345 - 4351
[3] Journal of Organometallic Chemistry, 2008, vol. 693, # 23, p. 3504 - 3508
Preparation of (3-(Dimethylamino)propyl)triphenylphosphonium bromide hydrobromide salt. To a suspension of 3-bromopropyltriphenylphosphonium bromide (1.0 g, 2.1 mmol) in ethanol (5 mL) was added a solution of 40percent dimethylamine in water (3 mL) at room temperature. The mixture was stirred and heated at 100 °C for 30 min in a sealed microwave tube. After the reaction mixture was concentrated under reduced pressure, the solid residue was recrystallized in acetonitrile to afford (3- (dimethylamino)propyl)triphenylphosphonium bromide hydrobromide salt (0.90 g, 82percent) as a white solid, and was used in the following step. ESI MS m/z 348.3(Ph3PCH2CH2CH2NMe2)+.
74.2%
Stage #1: at 20℃; for 1.5 h; Heating / reflux Stage #2: With Acetyl bromide In ethanol at 0 - 25℃;
Example 4; Synthesis of the Wittig Reagent 3-dimethylaminopropyltriphenylphosphonium Bromide *HBr (Olo-IM4) To a stirred suspension of 3-bromopropyltriphenylphosphonium bromide (Olo-IM3) (420 g, 0.90 mol) in absolute ethanol (664 g) a solution of dimethylamine in absolute ethanol (368 g, 2.69 mol, assay: 33percent) was added slowly within 30 minutes at room temperature. After complete addition the suspension was stirred 1 hour at reflux whereupon a solution was obtained. The solution was cooled to a temperature of 0-10° C. and acetyl bromide (202.7 g, 1.65 mol) was added dropwise until the pH was 1, and the resulting suspension was allowed to warm to 20-25° C. After the white suspension was filtered the wet product washed with absolute ethanol (237 g) and then dried under vacuum (15 h, 70° C.) to give 3-dimethylaminopropyltriphenylphosphonium bromide*HBr (Olo-IM4) as a white solid (yield: 471.2 g, 0.77 mol, 85.1percent; HPLC assay: 83.2percent, HPLC purity: 98.72percent). The crude material (460 g, 0.75 mol; assay: 83.2percent) was further purified by suspending it in absolute ethanol (395 g) and stirring at reflux temperature. After addition of further absolute ethanol (435 g) all material was dissolved and the solution was allowed to cool to room temperature, with seeding at 69° C. to initiate crystallization. After 4 hours stirring at room temperature the product was filtered off, washed with ethanol (140 g) and then dried under vacuum (15 h, 70° C.) to give 3-dimethylaminopropyltriphenylphosphonium bromide*HBr (Olo-IM4) as a crystalline white solid (yield: 333.7 g, 0.66 mol, 87.2percent; HPLC assay >99.9percent, HPLC purity: 99.85percent, overall yield: 74.2percent).
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h; Inert atmosphere;
Stage #2: benzophenone In tetrahydrofuran at 70℃; Inert atmosphere;
47%
With potassium <i>tert</i>-butylate In tetrahydrofuran Inert atmosphere; Reflux;
(i) NaH, (ii) /BRN= 1238185/; Multistep reaction;
With potassium <i>tert</i>-butylate
With sodium hydride In tetrahydrofuran at 60℃;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; Inert atmosphere;
Stage #2: benzophenone In tetrahydrofuran at 70℃;
With potassium <i>tert</i>-butylate
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; Inert atmosphere;
Stage #2: benzophenone In tetrahydrofuran at 70℃; Inert atmosphere;
With sodium hydride In tetrahydrofuran; mineral oil at 70℃; for 18h;
With sodium hydride In tetrahydrofuran for 18h; Reflux;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h; Inert atmosphere;
Stage #2: benzophenone In tetrahydrofuran at 70℃; Inert atmosphere;
With sodium hydride; In tetrahydrofuran; at 20℃; for 4.5h;
The C4 salt (II) is introduced as initial charge at room temperature in THF (I). The sodium hydride (III) is washed 3x with in each case 100 ml of n-hexane, dried in the nitrogen stream and added. The white suspension is then stirred for 4.5 h at room temperature (conversion check via HPLC). Geranyl acetone (IV) is then added and the mixture is heated at 35 C. for 21 h. 500 ml of n-heptane are then added to the yellowish suspension. THF is then removed on a rotary evaporatot The remaining suspension is admixed with 500 ml of water/methanol and the phases are separated. The aqueous phase is extracted 2x with 250 1 of n-heptane. The combined organic phases are washed 6x with 250 ml water methanol in order to separate off formed Nal3r and TPPO. The organic phase is dried over sodium sulfate and concentrated on a rotary evaporator at 50 C/b mbat This gives 50.6 g of product of value in the form of a brown, clear oil.
Stage #1: 3-bromopropyltriphenylphosphonium bromide; dimethyl amine In isopropyl alcohol at 0 - 40℃; for 16.25h; Heating / reflux;
Stage #2: With potassium carbonate In water; isopropyl alcohol at 55 - 60℃; for 9h;
5.c
(c) From 3-Bromopropyltriphenylphosphonium Bromide with Gaseous Dimethylamine Into a stirred suspension of 3-bromopropyltriphenylphosphonium bromide (58.02 g, 125 mmol) in 2-propanol (400 g) gaseous dimethylamine (17.3 g, 383 mmol) was bubbled within 15 minutes at 0-10° C. After that, the suspension was heated to 35-40° C. and stirred for 16 hours. Then from the clear solution 183 g of solvent was distilled off under reduced pressure (58-61° C., 400 mbar). At 45-50° C., water (3.0 g) and K2CO3 (17.28 g, 125 mmol) were added. Under reduced pressure (400 mbar), the suspension was heated to 55-60° C. and stirred for 9 hours, during which time some solvent was distilled off and most of the dimethylamine was removed. The amount of the distilled solvent (65 g) was added again. The white suspension was cooled to 20-25° C., and stirred for 30-60 minutes. Then the suspension was filtered and washed with 2-propanol (55 g). The white solid (dry 24.15 g) was discarded. From the filtrate (291 g) a total of 183 g solvent was distilled off at 60-62° C. under reduced pressure (400 mbar). The residue was cooled to 20-25° C. and MTBE (202 g) was added. The white milky emulsion was seeded with Olo-IM4 (free base) crystals to initiate the crystallization. The crystallization proceeded very fast and then the white suspension was heated to reflux (55° C.) and stirred for 1 hour. Then the suspension was cooled to 20-25° C. and stirred for 3 hours. The product was filtered off, washed with MTBE (50 g) and dried under vacuum (12 h, 50° C.) to give 3-dimethylaminopropyltriphenylphosphonium
83%
In ethanol at 23℃; for 15h;
68%
Stage #1: 3-bromopropyltriphenylphosphonium bromide; dimethyl amine In ethanol; isopropyl alcohol at 20℃; for 0.916667h; Heating / reflux;
Stage #2: With potassium carbonate In ethanol; isopropyl alcohol for 3.5h; Heating / reflux;
5.b
(b) from 3-bromopropyltriphenylphosphonium Bromide (Olo-IM3) with Dimethylamine Solution To a stirred suspension of 3-bromopropyltriphenylphosphonium bromide (11.64 g, 25.1 mmol) in 2-propanol (78.5 g), a solution of dimethylamine in absolute ethanol (10.25 g, 75.0 mmol; assay: 33%) was added slowly within 10 minutes at room temperature. After complete addition the suspension was stirred for 45 minutes at reflux temperature, then 26.4 g of solvent was distilled off under reduced pressure (62° C., 500 mbar). After addition of K2CO3 (4.15 g, 30 mmol) the suspension was stirred at reflux temperature for 3.5 hours, then cooled to room temperature, filtered through celite (3 g), and the cake washed with 2-propanol (2×15.7 g). Under reduced pressure (45° C., 100 mbar), most of the solvent was removed to obtain a supersaturated product solution (25.1 g). Under stirring this solution was seeded with Olo-IM4 (free base) crystals to initiate the crystallization. To the white suspension MTBE (37 g) and cyclohexane (39 g) were added slowly and the suspension was overnight for complete crystallization. The product was filtered off, washed with MTBE (2×18.5 g) and dried under vacuum (7 h, 50° C.) to give 3-dimethylaminopropyltriphenylphosphonium bromide (Olo-IM4, free base) as a white, crystalline solid (yield: 7.53 g, 17.1 mmol, 68.0%, HPLC assay: 97.03%).
Preparation of (3-(Dimethylamino)propyl)triphenylphosphonium bromide hydrobromide salt. To a suspension of 3-bromopropyltriphenylphosphonium bromide (1.0 g, 2.1 mmol) in ethanol (5 mL) was added a solution of 40% dimethylamine in water (3 mL) at room temperature. The mixture was stirred and heated at 100 C for 30 min in a sealed microwave tube. After the reaction mixture was concentrated under reduced pressure, the solid residue was recrystallized in acetonitrile to afford (3- (dimethylamino)propyl)triphenylphosphonium bromide hydrobromide salt (0.90 g, 82%) as a white solid, and was used in the following step. ESI MS m/z 348.3(Ph3PCH2CH2CH2NMe2)+.
74.2%
Example 4; Synthesis of the Wittig Reagent 3-dimethylaminopropyltriphenylphosphonium Bromide *HBr (Olo-IM4) To a stirred suspension of 3-bromopropyltriphenylphosphonium bromide (Olo-IM3) (420 g, 0.90 mol) in absolute ethanol (664 g) a solution of dimethylamine in absolute ethanol (368 g, 2.69 mol, assay: 33%) was added slowly within 30 minutes at room temperature. After complete addition the suspension was stirred 1 hour at reflux whereupon a solution was obtained. The solution was cooled to a temperature of 0-10 C. and acetyl bromide (202.7 g, 1.65 mol) was added dropwise until the pH was 1, and the resulting suspension was allowed to warm to 20-25 C. After the white suspension was filtered the wet product washed with absolute ethanol (237 g) and then dried under vacuum (15 h, 70 C.) to give 3-dimethylaminopropyltriphenylphosphonium bromide*HBr (Olo-IM4) as a white solid (yield: 471.2 g, 0.77 mol, 85.1%; HPLC assay: 83.2%, HPLC purity: 98.72%). The crude material (460 g, 0.75 mol; assay: 83.2%) was further purified by suspending it in absolute ethanol (395 g) and stirring at reflux temperature. After addition of further absolute ethanol (435 g) all material was dissolved and the solution was allowed to cool to room temperature, with seeding at 69 C. to initiate crystallization. After 4 hours stirring at room temperature the product was filtered off, washed with ethanol (140 g) and then dried under vacuum (15 h, 70 C.) to give 3-dimethylaminopropyltriphenylphosphonium bromide*HBr (Olo-IM4) as a crystalline white solid (yield: 333.7 g, 0.66 mol, 87.2%; HPLC assay >99.9%, HPLC purity: 99.85%, overall yield: 74.2%).
Stage #1: 3-bromopropyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; for 1.5h;
Stage #2: 5-Methoxy-1-tetralone In tetrahydrofuran at 20℃; for 5h;
17
Reference Example 17 1-cyclopropylidene-5-methoxy-1,2,3,4-tetrahydronaphthalene Under ice-cooling, to an anhydrous tetrahydrofuran (200 ml) solution of (3-bromopropyl)triphenylphosphinium bromide (19.8 g), potassium t-butoxide (9.58 g) was added, followed by stirring at room temperature for 1.5 hours. To the reaction mixture, 5-methoxy-1-tetralone (5.0 g) was added, followed by stirring at room temperature for 5 hours. The reaction mixture was poured into a saturated aqueous ammonium chloride solution. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with saturated saline, dried with anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 10: 1) to thereby obtain the title compound (5.66 g) having the following physical data. TLC: Rf 0.86 (hexane: ethyl acetate = 10: 1); NMR(CDCl3): δ 7.56(d, J=7.8Hz, 1H), 7.13(t, J=7.8Hz, 1H), 6.70(d, J=7.8Hz, 1H), 3.83(s, 3H), 2.76(t, J=6.4Hz, 2H), 2.66-2.56(m, 2H), 1.94-1.80(m, 2H), 1.51-1.40(m, 2H), 1.12-1.02(m, 2H).
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran for 12h; Reflux;
Stage #2: 2-ethynyl-5-fluorobenzaldehyde In tetrahydrofuran for 5h; Reflux;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h; Inert atmosphere;
Stage #2: 2-ethynyl-5-fluorobenzaldehyde In tetrahydrofuran at 70℃; for 6h; Inert atmosphere;
Into a suspension of (3-bromopropyl)triphenylphosphonium bromide (16.27 g, 35 mmol) in 1,2-dimethoxylethane (150 mL) was added NaH (60%, 2.8 g, 70.0 mmol) and 2 drops of ethanol. It was stirred at 65 C. for 6.5 hours. <strong>[84348-37-8](S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acid</strong> (2.0 g, 8.72 mmol) was added. The mixture was further stirred 22 hours at 65 C. before being cooled to rt. Ice (10 g) was added to quench the reaction. After concentrated, the residue was partitioned (H2O-EtOAc). The organics were separated and extracted with K2CO3 (1 M, 10 mL). The combined aqueous phase was cooled with ice-water and acidified with HCl (concentrated) to pH 12. This cloudy mixture was extracted with EtOAc (30 mL×3). The combined organic phase was dried and concentrated to give a yellow oil (1.44 g) which was used directly in the next step.
Stage #1: (3-bromopropyl)triphenylphosphinium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h;
Stage #2: (2-aminophenyl)-(4-fluorophenyl)methanone In tetrahydrofuran at 70℃; for 12h;
With sodium hydride In tetrahydrofuran for 24h; Reflux;
Stage #1: (3-bromopropyl)triphenylphosphinium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h; Inert atmosphere;
Stage #2: (2-aminophenyl)-(4-fluorophenyl)methanone In tetrahydrofuran at 70℃; for 12h; Inert atmosphere;
Stage #1: (3-bromopropyl)triphenylphosphinium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h; Inert atmosphere;
Stage #2: (2-aminophenyl)-(4-fluorophenyl)methanone In tetrahydrofuran at 70℃; for 12h;
With sodium hydride In tetrahydrofuran for 24h; Reflux;
With sodium hydride In tetrahydrofuran at 75℃;
Stage #1: (3-bromopropyl)triphenylphosphinium bromide With sodium hydride In tetrahydrofuran at 65℃; for 12h; Inert atmosphere;
Stage #2: (2-aminophenyl)-(4-fluorophenyl)methanone In tetrahydrofuran at 65℃; for 12h; Inert atmosphere;
Stage #1: (3-bromopropyl)triphenylphosphinium bromide With sodium hydride In tetrahydrofuran; mineral oil at 65℃; for 4h; Inert atmosphere; Schlenk technique;
Stage #2: (2-aminophenyl)-(4-fluorophenyl)methanone In tetrahydrofuran; mineral oil at 65℃; for 8h; Inert atmosphere; Schlenk technique;
Stage #1: (3-bromopropyl)triphenylphosphinium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h;
Stage #2: (2-aminophenyl)(4-chlorophenyl)methanone In tetrahydrofuran at 70℃; for 12h;
With sodium hydride In tetrahydrofuran for 24h; Reflux;
Stage #1: (3-bromopropyl)triphenylphosphinium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h; Inert atmosphere;
Stage #2: (2-aminophenyl)(4-chlorophenyl)methanone In tetrahydrofuran at 70℃; for 12h;
With sodium hydride In tetrahydrofuran for 24h; Reflux;
Stage #1: (3-bromopropyl)triphenylphosphinium bromide With sodium hydride In tetrahydrofuran at 65℃; for 12h; Inert atmosphere;
Stage #2: (2-aminophenyl)(4-chlorophenyl)methanone In tetrahydrofuran at 65℃; for 12h; Inert atmosphere;
Stage #1: (3-bromopropyl)triphenylphosphinium bromide With sodium hydride In tetrahydrofuran; mineral oil at 65℃; for 4h; Inert atmosphere; Schlenk technique;
Stage #2: (2-aminophenyl)(4-chlorophenyl)methanone In tetrahydrofuran; mineral oil at 65℃; for 8h; Inert atmosphere; Schlenk technique;
Intermediate A3. Step A3a. Into a suspension of 3-bromopropyltriphenyl phosphonium bromide (41.03 g, 88 mmol) in 1 ,2-dimethoxylethane (200 mL) was added NaH (60%, 7.04 g, 176.0 mmol) and 2 drops ethanol. The mixture was stirred at 65 C for 6.5 hours. (S)-l-(tert-butoxy- carbonyl)-4-oxopyrrolidine-2-carboxylic acid (5.05 g, 22.0 mmol) was added. The mixture was further stirred 2 days at 65 C before cooled and quench with ice. After being concentrated, the residue was partitioned (H20 - EtOAc). The organic phase was separated and extracted with K2CO3 (1 N, 10 mL). The combined aqueous phase was cooled in an ice/water bath, HC1 (Cone.) was added to bring the pH to 1 to 2. This cloudy mixture was extracted with EtOAc (x 3). The combined organic phase was dried (Na2S04) and concentrated to give yellow oil and was used directly in the next step. Step A3b. The solution of the crude product from step A3 a in benzene/MeOH (20 mL/20 mL) was treated with (trimethylsilyl)diazomethane solution (2.0 M in hexanes) in small portions until no more the nitrogen gas was generated. The reaction was concentrated and was purified by chromatography (silica, EtOAc -hexanes) to afford a colorless oil (4.62 g, 78% over two steps, a mixture of olefin regio isomers). ESIMS m/z =168.10 [M- Boc+2H]+. Step A3c. The solution of the compound from step A3b (4.62 g, 177.2 mmol) in MeOH (40 mL) was treated with ruthenium (5 wt% on carbon, 250 mg) under hydrogen (60 psi) at room temperature for 1 day. The mixture was passed through a short plug of silca gel column and was concentrated to afford a light yellow oil (4.78 g) and was used directly in the next step. ESIMS m/z =170.10 [M-Boc+2H]+. Step A3d. The solution of the crude compound from step A3c in EtOH (25 mL) and water (20 mL) was added LiOH monohydrate (720 mg, 17.05 mol) at room temperature overnight before was concentrated to give a yellow oil. This crude product was dissolved in water, washed with MTBE, and was brought to pH 2 by adding HC1 (4 M). The resulting mixture was extracted with EtOAc and CH2CI2. The combined organic phase was dried (Na2S04) and concentrated to give a pale yellow syrup (4.32 g, 90% for two steps), which slowly solidified upon standing at room temperature. ESIMS m/z =156.09 [M- Boc+2H]+.
tert-butyl 4-(cyclopropylidenemethyl)piperidine-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86%
Stage #1: (3-Brompropyl)triphenylphosphoniumbromid With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 0.75h; Inert atmosphere;
Stage #2: tert butyl 4-formylpiperidine-1-carboxylate In tetrahydrofuran at 0 - 20℃; Inert atmosphere;
Piperidines 6, 9, 14, 15, and 21: General Procedure
General procedure: Under argon, t-BuOK (27.0 g, 0.24 mol) was added in one portion to a stirred and cooled (0 °C) solution of the appropriate phosphonium salt 3a or 3b (0.12 mol) in anhyd THF (600 mL), and the mixture was stirred at 0 °C for 45 min. A solution of the appropriate ketone or aldehyde (0.10 mol) in anhyd THF (60 mL) was added dropwise to the stirred mixture, keeping the temperature at 0 °C (there was a very slight exothermic effect during the addition). The mixture was then warmed to r.t. and stirred overnight. Insoluble inorganic materials were removed by filtration, and the filtrate was evaporated in vacuo. The oily residue was triturated with hexane (300 mL), resulting in an abundant precipitate (Ph3PO). This was filtered off, and the filtrate was evaporated in vacuo to give crude alkene. Further distillation under reduced pressure afforded the pure compounds as oils, most of which solidified upon standing.
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h; Inert atmosphere;
Stage #2: 1-(4-tolylsulfonyl)indole-3-carboxaldehyde In tetrahydrofuran at 70℃; Inert atmosphere;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 65 - 70℃; Inert atmosphere;
Stage #2: 1-(4-tolylsulfonyl)indole-3-carboxaldehyde In tetrahydrofuran for 6h; Inert atmosphere; Reflux;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h;
Stage #2: (2-aminophenyl)(2-chlorophenyl)methanone In tetrahydrofuran at 70℃; for 12h;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; Inert atmosphere;
Stage #2: 2-amino-4-chlorobenzophenone In tetrahydrofuran at 70℃; Inert atmosphere;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; for 12h; Inert atmosphere;
Stage #2: 2-amino-5-methylbenzophenone In tetrahydrofuran at 70℃; for 12h;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; Inert atmosphere;
Stage #2: 3-fluorobenzophenone In tetrahydrofuran at 70℃;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran; hexane; mineral oil at 20℃; for 4.5h; Inert atmosphere;
Stage #2: pseudo-ionone In tetrahydrofuran; hexane; mineral oil at 35℃; for 21h;
2 Example 2: Wittig reaction starting from TPP-bromopropane salt using NaH
C4 salt (II) is introduced into THF (I) at room temperature as initial charge. Sodium hydride (III) washed three times (3 ×) in each case with 100 ml of n-hexane was added under stream of nitrogen. After that, the white suspension was stirred for 4.5 h at room temperature (confirmation by HPLC). After that, geranyl acetone (IV) was added, and the mixture was heated at 35 ° C for 21 h. Thereafter, 500 ml of n-heptane was added to the yellowish suspension. Then THF was removed with a rotary evaporator. The remaining suspension was mixed with 500 ml of water / methanol, the phases were separated, and the aqueous phase was extracted twice with (2 ×) 250 ml of n-heptane. The combined organic phases were washed six times (6 ×) with 250 ml of water / methanol, NaBr and TPPO obtained were separated, the organic phase was dried over sodium sulfate, concentrated at 50 ° C./10 mbar with a rotary evaporator to give 50.6 g of valuable product in the form of a brown clear oil.
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran; mineral oil at 80℃; for 8h; Inert atmosphere;
Stage #2: 2-iodobenzophenone In tetrahydrofuran; mineral oil at 80℃; for 8h; Inert atmosphere;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran for 12h; Inert atmosphere; Heating;
Stage #2: 2-iodobenzophenone In tetrahydrofuran Inert atmosphere; Heating;
In tetrahydrofuran at 80℃;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran for 2h; Reflux; Inert atmosphere;
Stage #2: 2-iodobenzophenone In tetrahydrofuran for 3h; Inert atmosphere;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 70℃; Inert atmosphere;
Stage #2: 2-iodobenzophenone In tetrahydrofuran at 70℃; Inert atmosphere;
2-(benzyloxy)-4-bromo-1-(cyclopropylidenemethyl)benzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
Stage #1: 3-bromopropyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran for 2.5h; Reflux;
Stage #2: 2-(benzyloxy)-4-bromobenzaldehyde In tetrahydrofuran at 65℃;
Stage #1: 3-bromopropyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran at 75℃; for 12h;
Stage #2: 2-bromo-6-methylbenzaldehyde In tetrahydrofuran at 75℃; for 12h;
Stage #1: (3-bromopropyl)triphenylphosphinium bromide With sodium hydride In tetrahydrofuran; mineral oil at 65℃; for 4h; Inert atmosphere; Schlenk technique;
Stage #2: 2-amino-3',5'-dimethylbenzophenone In tetrahydrofuran; mineral oil at 65℃; for 8h; Inert atmosphere; Schlenk technique;
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