Structure of 33670-32-5
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| CAS No. : | 33670-32-5 |
| Formula : | C20H20BrOP |
| M.W : | 387.25 |
| SMILES Code : | COC[P+](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3.[Br-] |
| English Name : | (Methoxymethyl)triphenylphosphonium bromide |
| MDL No. : | MFCD00075442 |
| InChI Key : | NOCGROPYCGRERZ-UHFFFAOYSA-M |
| Pubchem ID : | 2773654 |
* 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 |
|---|---|---|
| 73% | Stage #1: methoxymethyltriphenylphosphonium bromide With n-butyllithium In tetrahydrofuran at 0℃; for 0.5h; Stage #2: methyl (3,4,5-trimethoxyphenyl) ketone In tetrahydrofuran at 0℃; for 0.5h; | |
| 73% | Stage #1: methoxymethyltriphenylphosphonium bromide With n-butyllithium In tetrahydrofuran at 0℃; for 0.5h; Stage #2: methyl (3,4,5-trimethoxyphenyl) ketone In tetrahydrofuran at 0℃; for 0.5h; | 5 To a flame dried 250 mL round-bottom flask was added methoxymethyltriphenylphosphonium bromide (10.28 g, 30.0 mmol). THF (100 mL) was added and the solution cooled to 0° C. n-BuLi (14.0 mL, 30.0 mmol, 2.2 M) was added dropwise and the solution stirred at 0° C. for 30 min. 3,4,5-Trimethoxyacetophenone (5.26 g, 25.0 mmol) in THF (25 mL) was added dropwise. The reaction was stirred at 0° C. for 30 min, and then water (30 mL) was added. The layers were separated, and the aqueous layer was extracted with Et2O (3×20 mL). The combined organics were washed with brine (30 mL), dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash chromatography (SiO2, 50 g) using 5% EtOAc in hexanes as eluent to afford the enol ether (4.35 g, 73%). The enol ether (4.35 g, 18.26 mmol) was dissolved in THF (37.0 mL). Concentrated HCl (3.0 mL) was added and the solution heated to reflux. The solution was stirred at reflux for 3 h and allowed to cool to room temperature. Water (10 mL) was added, and the organics were washed with sat. NaHCO3 (10 mL) and brine (10 mL), dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash chromatography (SiO2, 50 g) using 20% EtOAc in hexanes as the eluent to afford 2-(3,4,5-trimethoxyphenyl)propanal (3.82 g, 93%). Spectra were the identical to literature values CBr4 (8.47 g, 25.55 mmol) was dissolved in DCM (150 mL) and cooled to 0° C. Ph3P (13.4 g, 51.09 mmol) was added and the solution stirred at 0° C. for 5 min. 2-(3,4,5-trimethoxyphenyl)propanal (3.82 g, 17.03 mmol) in DCM (20 mL) was added dropwise. The reaction was stirred at 0° C. for 30 min and then poured into ice-cooled Et2O (500 mL). The solids were filtered through Celite and washed with Et2O (3×50 mL). The combined organics were concentrated. The residue was filtered through a plug of silica and washed with hexanes (100 mL) followed by 10% EtOAc in hexanes (5×100 mL). The combined organics were concentrated to give the intermediate dibromide (4.86 g, 75%) which was used directly for the next reaction. Mg (0.621 g, 25.57 mmol) was suspended in THF (2.0 mL). 1,2-Dibromoethane (0.442 mL, 5.12 mmol) was added and the reaction stirred at 25° C. for 30 min. The dibromide (4.86 g, 12.79 mmol) in THF (11.0 mL) was added dropwise and the solution heated to reflux where it was stirred for 1 h. The solution was cooled to room temperature and the solvent removed. The residue was purified by flash chromatography (SiO2, 150 g) using 10% EtOAc in hexanes as the eluent to afford 5-(But-3-yn-2-yl)-1,2,3-trimethoxybenzene as a colorless oil (1.97 g, 70%): Rf=0.29 (4:1, Hex:EtOAc); 1H NMR (CDCl3) δ 6.62 (s, 2H), 3.88 (s, 6H), 3.84 (s, 3H), 3.74-3.69 (m, 1H), 2.29 (d, J) 2.7 Hz, 1H), 1.52 (d, J) 7.1 Hz, 3H); 13C NMR (CDCl3) δ 153.4, 138.5, 136.9, 104.0, 104.0, 87.2, 70.5, 61.0, 56.3, 32.1, 24.5; HRFAB[M+Li]227.1243 (calculated C13H16O3Li: 227.1259). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 93% | Stage #1: methoxymethyltriphenylphosphonium bromide With Lithium 1,1,1,3,3,3-hexamethyldisilazide In tetrahydrofuran at 0℃; for 1h; Stage #2: 2-chloro-4-(4-chlorophenoxy)benzaldehyde In tetrahydrofuran | 1.1-1 The solution of (methoxymethyl)triphenylphosphonium bromide (45.1 g, 0.31 mol) in THF (400 mL), LiHMDS (130 mL, 0.13 mol) was added at 0 °C. The reaction mixture was stirred for 1 h and then, a solution of 2-chloro-4-(4-chlorophenoxy)benzaldehyde (32.3 g, 0.12 mol) in THF was added dropwised. The reaction mixture was stirred overnight, which was quenched by the addition of an aq. NH4CI and extracted with MTBE. Upon separation, the organic phase was washed with brine, dried over Na2S04 and concentrated. The crude was purified by silica gel column chromatography (PE : EtOAc = 400 : 1 ) to give 2-chloro-4-(4-chlorophenoxy)-1 -[(E)-2- methoxyvinyl]benzene (33.1 g, 93%) H-NMR (CDCI3, 400 MHz) 5=8.1 (d, J = 8.8 Hz, 1 H), 7.3- 7.2 (m, 2 H), 7.1 (m, 1 H), 7.0 (m, 2 H), 6.9 (m, 1 H), 6.3 (d, J = 7.3 Hz, 1 H), 5.6 (d, J = 7.3 Hz, 1 H), 3.9 (s, 3 H) 3.8 (s, 3 H) |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 81.8% | Stage #1: methoxymethyltriphenylphosphonium bromide With sodium hexamethyldisilazane In tetrahydrofuran at 0℃; for 1h; Stage #2: benzyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate In tetrahydrofuran at 20℃; for 2h; | 14-1 benzyl 2- (methoxymethylene) -7-azaspiro [3.5] nonane-7-carboxylate To a solution (methoxymethyl) triphenylphosphonium bromide (338 mg, 0.87 mmol) in THF (5 mL) was added NaHMDS (1 mL, 1 mmol, 1M in THF) at 0. After stirring for 1h at 0, benzyl 2-oxo-7-azaspiro [3.5] nonane-7-carboxylate (200 mg, 0.73 mmol) was added to the mixture, then the resulting mixture was stirred for 2h at rt. The reaction was quenched with aq NH4Cl (5 mL) and extracted with EtOAc (3 x 10 mL) . The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by reverse-phase HPLC (mobile phase: methanol/water (10mM NH4HCO3) ) to give benzyl 2- (methoxymethylene) -7-azaspiro [3.5] nonane-7-carboxylate (180 mg, 81.8) . LRMS m/z (M+H) 302.2 found, 302.2 required. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 66% | Stage #1: methoxymethyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: methyl 3-acetylbicyclo<1.1.1>pentane-1-carboxylate In tetrahydrofuran at 0 - 20℃; for 1.5h; Schlenk technique; Inert atmosphere; | 3 Add (methoxymethyl)triphenylphosphonium chloride (5.4mmol, 1.5equiv) to a 50mL Shrek tube, and replace with nitrogen three times. Add 10 mL of tetrahydrofuran under nitrogen protection. Add potassium tert-butoxide (600mg, 5.4mmol, 1.5equiv) in batches at 0°C and react at room temperature for 30 minutes. The temperature was lowered to 0°C, and compound 3-2 (600 mg, 3.6 mmol, 1 equiv) was added to the above system. React at room temperature for 1.5h. After the reaction was completed, it was quenched with 100 mL saturated ammonium chloride solution, extracted three times with 100 mL ethyl acetate, and the combined organic phase was washed once with 150 mL saturated brine. Dry the organic phase with anhydrous sodium sulfate for 15 minutes, the anhydrous sodium sulfate was removed by filtration, the filtrate was spin-dried and the crude product was purified by column chromatography (ethyl acetate/petroleum ether, 0→15%) to obtain 460 mg of compound 3-3 (66%) as a yellow oily liquid. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | Stage #1: methoxymethyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: C19H14FNO In tetrahydrofuran at 20℃; for 3h; Schlenk technique; Inert atmosphere; | 5 The compound (methoxymethyl)triphenylphosphonium chloride (797.6mg, 2.0mmol, 3.0equiv) was added to a 50mL Shrek tube and replaced with nitrogen three times. Then add dry tetrahydrofuran (4.0mL) to dilute, then slowly add 1mol/L potassium tert-butoxide solution (167.9mg, 2.3mmol, 3.3equiv) in tetrahydrofuran (167.9mg, 2.3mmol, 3.3equiv) under ice-bath stirring, and stir under ice-bath for 30 minute. Next, compound 11-4 (200.0mg, 0.7mmol, 1.0equiv) was dissolved in 3.0mL of tetrahydrofuran solution and slowly dripped into the above system under ice bath stirring. After dripping, the temperature was raised to room temperature, and then stirred for 3.0 hours. The reaction was monitored by LCMS and found to be complete. The reaction system was slowly poured into a saturated aqueous solution of ammonium chloride under stirring in an ice bath, and then extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the organic phase was spin-dried. After spin-drying, the crude product was purified by column chromatography [ethyl acetate/petroleum ether, 0%→50%], 200 mg (91%) of compound 11-5 was obtained as a pale yellow solid. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 72.1% | Stage #1: methoxymethyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: methyl 4-acetylcubane-1-carboxylate In tetrahydrofuran at 0 - 20℃; for 1h; Schlenk technique; Inert atmosphere; | 3 Add (methoxymethyl)triphenylphosphonium chloride (903.0mg, 2.9mmol, 1.5equiv) into a 50mL Shrek tube, and replace with nitrogen three times, add 6.0 mL of tetrahydrofuran under nitrogen protection. Add potassium tert-butoxide (330mg, 2.97mmol, 1.5equiv) in batches at 0°C, after reacting at room temperature for 30 minutes, the temperature was lowered to 0°C, and compound 13-2 (400 mg, 2.0 mmol, 1.0 equiv) was added to the above system. React at room temperature for 1.0h. After the reaction is complete, it is quenched with 100 mL saturated ammonium chloride solution, extracted with ethyl acetate three times, and the combined organic phase is washed once with 150 mL saturated brine. The organic phase was dried with anhydrous sodium sulfate for 15min, filtered to remove the anhydrous sodium sulfate, after the filtrate was spin-dried, the crude product was purified by column chromatography (ethyl acetate/petroleum ether, 0→20%), 328 mg of compound 13-3 (72.1%) was obtained as a pale yellow oily liquid. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | Stage #1: methoxymethyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 0.333333h; Inert atmosphere; Stage #2: 2-formyl-4,5-dimethoxyphenethyl methanesulfonate In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere; | 4.3. 4,5-dimethoxy-2-(2-oxoethyl)phenethylmethanesulfonate (7) Potassium t-butoxide (0.59 g, 5.27 mmol) was added to a stirred solution of methoxymethyltriphenylphosphonium bromide (2.13 g, 6.25 mmol) in dry THF (15 mL) at 0 °C under nitrogen atmosphere and the stirring was continued at this temperature for 20 min, after which the aldehyde 9 (0.95 g, 3.29 mmol) in dry THF (12 mL) was added to the reaction mixture dropwise and further stirring was continued at room temperature for 2 h. After the complete disappearance of starting material on TLC, the reaction mixture was quenched with saturated NH4Cl solution (10 mL). The product was extracted with EtOAc (3 × 15 mL), and dried over anhydrous Na2SO4. The solvents were removed under reduced pressure, and the crude product was purified through column chromatography (85:15 petroleum ether/EtOAc) to get enol ether as a colorless oil (0.93 g, 90%). The enol ether was dissolved in THF (15 mL) and 2 N HCl (5 mL) was added dropwise to the reaction mixture and stirred for 6 h. The product was extracted with EtOAc (3 × 15 mL), and dried over anhydrous Na2SO4. The solvents were removed under reduced pressure and the crude product was purified through column chromatography (75:25 petroleum ether/EtOAc) to get an aldehyde 7 as a colorless oil (0.81 g, 82%); 1H NMR (CDCl3, 400 MHz) δ 9.72 (t, J = 1.9 Hz, 1H), 6.74 (s, 1H), 6.64 (s, 1H), 4.30 (t, J = 7.1 Hz, 2H), 3.86 (s, 3H), 3.85 (s, 3H), 3.70 (d, J = 1.9 Hz, 2H), 2.96 (t, J = 7.1 Hz, 2H), 2.90 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 199.0, 148.7, 148.4, 127.5, 122.7, 114.0, 113.4, 69.7, 56.1, 56.0, 47.9, 37.4, 32.5 ppm; FTIR (thin film): 2938, 2836, 2728, 1720, 1609, 1519, 1466 cm-1. HRMS (ESI-TOF) m/z [M + Na]+ calcd. for C13H18NaO6S 325.0722, found 325.0726. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 81.46% | Stage #1: methoxymethyltriphenylphosphonium bromide In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: tert-butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; | 5.1 Step 1: Synthesis of compound 5b Under nitrogen protection, (methoxymethyl) triphenylphosphine bromide (11.49 g, 37.4 mmol) was dissolved in ultra-dry tetrahydrofuran (50 mL) solution, followed by the slow addition of di(trimethylsilyl) lithium amide (37.4 mmol, 7 mL) at -78 ° C. After reacting for 30 min, compound 5a (5 g, 18.70 mmol) was added, followed by the continued reaction for two hours. The reaction mixture was poured into 100 mL of water and extracted with ethyl acetate (30 mL × 2). The combined organic phase was washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column to obtain compound 5b (4.5 g, yield: 81.46%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | With potassium <i>tert</i>-butylate In tetrahydrofuran at 50℃; | 12 Compound 1-3 In anhydrous tetrahydrofuran (10.0 mL) of compound l-2 (0.70 g, 4.31 mmol), methoxymethyl triphenylphosphonium bromide (2.20 g, 5.19 mmol) and potassium tert-butoxide (0.70 g, 6.42 mmol) were added. The reaction was heated to 50 degrees and stirred overnight. LCMS monitoring showed that the reaction was complete. The reaction solution was quenched with water and extracted with ethyl acetate (30 mL*3). The combined organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. The concentrated crude product was purified by normal phase silica gel column to obtain compound l-3 (0.80 g, yield 85%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 87.4% | Stage #1: methoxymethyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: tert-butyl (1R,5S)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate In tetrahydrofuran at 0 - 20℃; for 13h; Inert atmosphere; | Step 1: (methoxymethyl)triphenylphosphonium bromide(1.93 g, 4.97 mmol) was dissolved in THF (20 mL), then t-BuOK (1 M, 5.47 mL) was added at 0 °C under nitrogen and the mixture was stirred for 1 h. The tert-butyl (1R,5S)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (800 mg, 1.66 mmol) obtained in Step 1 was dissolved in THF (8 mL) and added to the reaction mixture, which was stirred at 0 °C for 1 h and then at room temperature for 12 h under nitrogen. At 0 °C, water (50 mL) was added to quench the reaction and the mixture was extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to give tert-butyl (R)-1-(2-methoxyvinyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (0.74 g, 87.4% yield) as a yellow oil. |