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Structure of 74733-30-5
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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| CAS No. : | 74733-30-5 |
| Formula : | C9H8BrClO2 |
| M.W : | 263.52 |
| SMILES Code : | O=C(OC)C1=CC=C(CBr)C(Cl)=C1 |
| MDL No. : | MFCD10566565 |
| InChI Key : | XTZCVWDSGCVDFI-UHFFFAOYSA-N |
| Pubchem ID : | 22027761 |
| GHS Pictogram: |
|
| Signal Word: | Danger |
| Hazard Statements: | H302-H314 |
| Precautionary Statements: | P260-P264-P270-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501 |
| Class: | 8 |
| UN#: | 3261 |
| Packing Group: | Ⅱ |
| Num. heavy atoms | 13 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.22 |
| Num. rotatable bonds | 3 |
| Num. H-bond acceptors | 2.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 55.57 |
| TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.58 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.96 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.87 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.25 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.36 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.0 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-3.48 |
| Solubility | 0.0868 mg/ml ; 0.00033 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-3.18 |
| Solubility | 0.176 mg/ml ; 0.000668 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.35 |
| Solubility | 0.0118 mg/ml ; 0.0000448 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.81 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.89 |
* 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 |
|---|---|---|
| 92% | With tert.-butylhydroperoxide; cetyltrimethylammonim bromide; potassium bromide; In water; at 120℃; under 750.075 Torr;Microwave irradiation; | General procedure: The reaction mixture was treated in a controlled microwavesynthesizer (Biotage Initiator+SP Wave model, 0-200 W at2.45 GHz, capped at 60 W during steady state) for severalminutes (the reaction attained 120 C at 1 bar pressure). Thefinal products were isolated by column chromatographyusing an EtOAc-hexane gradient |
| 84% | With 2,2'-azobis(2-methylpropionitrile); N-Bromosuccinimide; In tetrachloromethane; for 18h;Heating / reflux; | To a solution of methyl 3-chloro-4-methylbenzoate (5.0 g, 27.1 mmol) in carbon tetrachloride (50 ml) were added N-bromosuccinimide (5.8 g, 32.0 mmol) and 2,2'-azo-bis(2-methylpropionitrile) (0.442 g, 2.70 mmol). The mixture was heated at reflux for 18 h, then allowed to cool to room temperature and concentrated in vacuo. The residue was purified by flash chromatography on silica (eluant pet. ether ? 5% ethyl acetate/95% pet. ether) to give an oil identified as methyl 4-bromomethyl-3-chlorobenzoate (5.96 g, 84%). |
| 84% | With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 18h;Heating / reflux; | To a solution of methyl 3-chloro-4-methylbenzoate (5.0g, 27.1mmol) in carbon tetrachloride (50ml) were added NBS (5.8g, 32.0mmol) and AIBN (0.442g, 2.70mmol). The mixture was stirred at reflux for 18h. The mixture was allowed to cool to room temperature and then concentrated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 0:100 to 5:95); yield 5.96g (84%). |
| 84% | With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 18h;Heating / reflux; | To a solution of methyl 3-chloro-4-methylbenzoate (5.0 g, 27.1 mmol) in carbon tetrachloride (50 ml) were added NBS (5.8 g, 32.0 mmol) and AIBN (0.442 g, 2.70 mmol).. The mixture was stirred at reflux for 18 h.. The mixture was allowed to cool to room temperature and then concentrated in vacuo.. The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 0:100 to 5:95); yield 5.96 g (84%). |
| 75% | With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 4h;Heating / reflux; | step 1-A mixture of 184a (2 mmol), NBS (2.2 mmol) and AIBN (100 mg) in CCl4 (20 mL) was heated at reflux for 4 h. The mixture was cooled, filtered and the filtrate was concentrated in vacuo. The residue was purified by SiO2 chromatography to afford 0.395 g (75%) of 184b. |
| 5.96 g (84%) | With N-Bromosuccinimide; azobisisobutyronitrile; In tetrachloromethane; | A1. Methyl 4bromomethyl-3-chlorobenzoate To a solution of methyl 3-chloro-4-methylbenzoate (5.0 g, 27.1 mmol) in carbon tetrachloride (50 ml) were added NBS (5.8 g, 32.0 mmol) and AIBN (0.442 g, 2.70 mmol). The mixture was stirred at reflux for 18 h. The mixture was allowed to cool to room temperature and then concentrated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 0:100 to 5:95); yield 5.96 g (84%). |
| With N-Bromosuccinimide;benzoic peroxyanhydride; In tetrachloromethane; | (2) Preparation of methyl 4-bromomethyl-3-chlorobenzoate Methyl 4-methyl-3-chlorobenzoate (4.5 g, 0.024 mol) was dissolved in carbon tetrachloride (100 ml), and thereto were added N-bromosuccinimide (4.8 g, 0.026 mol) and a catalytic amount of perbenzoic anhydride. The mixture was heated and refluxed under nitrogen atmosphere for 2 hours, allowed to cool, and the precipitate was separated by filtration. The filtrate was concentrated, and separated and purified by using a silica-gel column chromatography (ethyl acetate:n-hexane=1:20) to give the title compound (4.7 g, 0.018 mol) (yield 75%). NMR (CDCl3) delta: 8.04 (s, 1H), 7.91 (bd, J=8.13Hz, 1H), 7.50 (d, J=7.92Hz, 1H), 4.58 (s, 2H), 3.92 (s, 3H) | |
| 5.96 g (84%) | With N-Bromosuccinimide; azobisisobutyronitrile; In tetrachloromethane; | A1. Methyl 4-bromomethyl-3-chlorobenzoate To a solution of methyl 3-chloro-4-methylbenzoate (5.0 g, 27.1 mmol) in carbon tetrachloride (50 ml) were added NBS (5.8 g, 32.0 mmol) and AIBN (0.442 g, 2.70 mmol). The mixture was stirred at reflux for 18 h. The mixture was allowed to cool to room temperature and then concentrated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 0:100 to 5:95); yield 5.96 g (84%). |
| With N-Bromosuccinimide;dibenzoyl peroxide; In tetrachloromethane; for 6h;Reflux; | (2-Chloro-4-(methoxycarbonyl)benzyl)triphenylphosphonium bromideMethyl 3-chloro-4-methylbenzoate (2.20 g, 11.96 mmol) was dissolved in carbon tetrachloride (30 mL) and N-bromosuccinimide (2.10 g, 11.80 mmol) was added followed by a catalytic amount of benzoyl peroxide (25 mg). The reaction mixture was refluxed for 6h. (ca. 90% conversion). After cooling to room temperature, a precipitate was filtered. The filtrate was concentrated to give crude brominated intermediate (3.20 g), which was used for the next step without further purification. | |
| With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 6h;Reflux; | Methyl 3-chloro-4-methylbenzoate (2.20 g, 11.96 mmol) was dissolved in carbon tetrachloride (30 mL) and N-bromosuccinimide (2.10 g, 11.80 mmol) was added followed by a catalytic amount of benzoyl peroxide (25 mg). The reaction mixture was refluxed for 6 h. (ca. 90% conversion). After cooling to room temperature, a precipitate was filtered. The filtrate was concentrated to give crude brominated intermediate (3.20 g), which was used for the next step without further purification. | |
| With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; at 80℃; | Methyl 3-chloro-4-methylbenzoate (0.30 mL, 2.0 mmol) was dissolved in carbon tetrachloride (5 mL), N-bromosuccinimide (0.39 g, 2.2 mmol) and benzoyl peroxide (48 mg, 0.20 mmol) were added, and the mixture was stirred at 80 C. overnight. The reaction mixture was filtered and concentrated under reduced pressure, 8 mol/L ammonia-methanol solution was added to the obtained residue, and the mixture was stirred at room temperature for 90 min. The reaction mixture was concentrated under reduced pressure, and the obtained residue was dissolved in dichloromethane (5 mL). A-1 (0.36 g, 1.2 mmol), WSC hydrochloride (0.29 g, 1.5 mmol) and HOAt (0.16 g, 1.2 mmol) were added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by reversed-phase high performance liquid chromatography (water-acetonitrile, each containing 0.1% trifluoroacetic acid) to give the title compound (0.40 g, 0.84 mmol, 42%). | |
| With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 100℃; for 15h; | To a solution of methyl 3-chloro-4-methyl-benzoate (22.5 g, 121 mmol) and 2,2- azobisisobutyronitrile (2.00 g, 12.2 mmol) in carbon tetrachloride (300 mL) was added 1- bromopyrrolidine-2,5-dione (23.8 g, 134 mmol) portion wise. The mixture was heated to 100 C and stirred at 100 C for 15 hours. On completion, the mixture was concentrated in vacuo to give a solid. The solid was washed with water (200 mL) and extracted with DCM (2 X 150 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuum to give a residue. The residue was purified with silica gel chromatograph (petroleum ether: ethyl acetate = 100: 1) to give the title compound. NMR (400MHz, CDCh) delta = 7.99 (d, J = 1.5 Hz, 1H), 7.84 (dd, 7= 1.6, 8.0 Hz, 1H), 7.45 (d, J= 8.0 Hz, 1H), 4.53 (s, 2H), 3.86 (s, 3H). |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With ammonia; In ethanol; at 20℃; for 1h; | To a saturated solution of ammonia in ethanol (170ml) was added <strong>[74733-30-5]methyl 4-bromomethyl-3-chlorobenzoate</strong> from Example Al (5.5g, 20.9mmol). The mixture was stirred at room temperature for lhr and then concentrated in vacuo. The residue was triturated with diethyl ether and the resultant white crystals were filtered off and washed with more diethyl ether. To a solution of this solid in water (100ml) were added solutions of (BOC)20 (5.0g, 23.0mmol) in dioxan (100ml) and sodium hydroxide (1.86g, 46.0mmol) in water (100ml).The mixture was stirred at room temperature for 18h and then concentrated in vacuo. The aqueous residue was acidified with citric acid and extracted with chloroform/IP A. The organic layer was washed with water, dried over MgS04, and concentrated in vacuo to give a white solid; yield 2.8g (67%). | |
| With ammonia; In methanol; at 20℃; for 1.5h; | Methyl 3-chloro-4-methylbenzoate (0.30 mL, 2.0 mmol) was dissolved in carbon tetrachloride (5 mL), N-bromosuccinimide (0.39 g, 2.2 mmol) and benzoyl peroxide (48 mg, 0.20 mmol) were added, and the mixture was stirred at 80 C. overnight. The reaction mixture was filtered and concentrated under reduced pressure, 8 mol/L ammonia-methanol solution was added to the obtained residue, and the mixture was stirred at room temperature for 90 min. The reaction mixture was concentrated under reduced pressure, and the obtained residue was dissolved in dichloromethane (5 mL). A-1 (0.36 g, 1.2 mmol), WSC hydrochloride (0.29 g, 1.5 mmol) and HOAt (0.16 g, 1.2 mmol) were added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by reversed-phase high performance liquid chromatography (water-acetonitrile, each containing 0.1% trifluoroacetic acid) to give the title compound (0.40 g, 0.84 mmol, 42%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 67% | To a saturated solution of ammonia in ethanol (170 ml) was added <strong>[74733-30-5]methyl 4-bromomethyl-3-chlorobenzoate</strong> from Example 4A (5.5 g, 20.9 mmol). The mixture was stirred at room temperature for 1 h and then concentrated in vacuo. The residue was triturated with diethyl ether and the resultant white crystals were filtered off and washed with more diethyl ether. To a solution of this solid in water (100 ml) were added solutions of di-tert-butyl dicarbonate (5.0 g, 23.0 mmol) in dioxan (100 ml) and sodium hydroxide (1.86 g, 46.0 mmol) in water (100 ml). The mixture was stirred at room temperature for 18h and then concentrated in vacuo. The aqueous residue was acidified with citric acid and extracted with chloroform/2-propanol. The organic layer was washed with water, dried over MgSO4, and concentrated in vacuo to give a white solid identified as 4-(tert-butyloxycarbonylaminomethyl)-3-chlorobenzoic acid (2.8 g, 67%). | |
| 67% | To a saturated solution of ammonia in ethanol (170 ml) was added <strong>[74733-30-5]methyl 4-bromomethyl-3-chlorobenzoate</strong> from Example A1 (5.5 g, 20.9 mmol).. The mixture was stirred at room temperature for 1 h and then concentrated in vacuo.. The residue was triturated with diethyl ether and the resultant white crystals were filtered off and washed with more diethyl ether.. To a solution of this solid in water (100 ml) were added solutions of (BOC)2O (5.0 g, 23.0 mmol) in dioxan (100 ml) and sodium hydroxide (1.86 g, 46.0 mmol) in water (100 ml).. The mixture was stirred at room temperature for 18 h and then concentrated in vacuo.. The aqueous residue was acidified with citric acid and extracted with chloroform/IPA. The organic layer was washed with water, dried over MgSO4, and concentrated in vacuo to give a white solid; yield 2.8 g (67%). | |
| With sodium hydroxide; ammonia; In 1,4-dioxane; ethanol; water; | A2. 4-(tert-Butyloxycarbonylaminomethyl)-3-chlorobenzoic acid To a saturated solution of ammonia in ethanol (170 ml) was added <strong>[74733-30-5]methyl 4-bromomethyl-3-chlorobenzoate</strong> from Example A1 (5.5 g, 20.9 mmol). The mixture was stirred at room temperature for 1 h and then concentrated in vacuo. The residue was triturated with diethyl ether and the resultant white crystals were filtered off and washed with more diethyl ether. To a solution of this solid in water (100 ml) were added solutions of (BOC)2O (5.0 g, 23.0 mmol) in dioxan (100 ml) and sodium hydroxide (1.86 g, 46.0 mmol) in water (100 ml). The mixture was stirred at room temperature for 18 h and then concentrated in vacuo. The aqueous residue was acidified with citric acid and extracted with chloroform/IPA. The organic layer was washed with water, dried over MgSO4, and concentrated in vacuo to give a white solid; yield 2.89 (67%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In N-methyl-acetamide; | a) methyl 4-(phthalimidomethyl)-3-chlorobenzoate A mixture of <strong>[74733-30-5]methyl 4-bromomethyl-3-chlorobenzoate</strong> 10 g, 38 mmol) and potassium phthalimide (9.85 g, 53 mmol) in dimethylformamide (65 mL) was stirred and heated to 85 C. for 2 h. The hot mixture was poured into ice water and the resulting solid was filtered, washed sequentially with water, ethanol and a small amount of ether and dried to give the title compound. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 44% | Part B. Methyl 3-Chloro-4-[(1-pyrrolidinyl)methyl]benzoate STR291 The title compound was prepared in 44% yield by essentially following the procedures outlined in the second part of Example 37, Part A, from <strong>[74733-30-5]methyl 4-bromomethyl-3-chlorobenzoate</strong> (Part A). FDMS 253 (M+); Anal. Calcd for C13 H16 ClNO2: C, 61.54; H, 6.36; N, 5.52. Found: C, 61.24; H, 6.11; N, 5.53. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 2.8 g (67%) | With sodium hydroxide; ammonia; In 1,4-dioxane; ethanol; water; | A2. 4-(tert-Butyloxycarbonylaminomethyl)-3-chlorobenzoic acid To a saturated solution of ammonia in ethanol (170 ml) was added <strong>[74733-30-5]methyl 4-bromomethyl-3-chlorobenzoate</strong> from Example A1 (5.5 g, 20.9 mmol). The mixture was stirred at room temperature for 1 hr and then concentrated in vacuo. The residue was triturated with diethyl ether and the resultant white crystals were fiflered off and washed with more diethyl ether. To a solution of this solid in water (100 ml) were added solutions of (BOC)2O (5.0 g, 23.0 mmol) in dioxan (100 ml) and sodium hydroxide (1.86 g, 46.0 mmol) in water (100 ml). The mixture was stirred at room temperature for 18 h and then concentrated in vacuo. The aqueous residue was acidified with citric acid and extracted with chloroform/IPA. The organic layer was washed with water, dried over MgSO4, and concentrated in vacuo to give a white solid; yield 2.8 g (67%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | With triethylamine; In dichloromethane; at 20℃; | step 2-A mixture of 32b (1 mmol), 184b (1 mmol) and TEA (0.1 mL) in DCM (2 mL) was stirred at RT overnight. The mixture was concentrated and purified by SiO2 chromatography to afford 0.467 g (80%) of 186a. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With N-Bromosuccinimide;dibenzoyl peroxide; In tetrachloromethane; at 80℃; | After stirring a suspension of 3-chloro-4-methyl-benzoic acid methyl ester (1.04 g, 5.61 mmol), l-bromo-pyrtauolidine-2,5-dione (3.26 g, 15.7 mmol) and benzoyl peroxide (100.2 mg, 0.88 mmol) in tetrachloromethane (68 mL) at 800C overnight the mixture was concentrated in vacuo and the residue was partitioned between EA (300 mL) and water (200 mL). The organic layer was washed with sat. NaHCtheta3 solution (1 x 200 mL), water (1 x 200 mL) and sat. NaCl solution (1 x 200 mL). The organic layer was dried over Na2SO4, filtered and <n="99"/>concentrated in vacuo. The residue, a mix of 4-bromomethyl-3-chloro-benzoic acid methyl ester and 4-dibromomethyl-3-chloro-benzoic acid methyl ester, was used in the following step without further purification. The residue (1.48 g, 5.61 mmol) was dissolved in acetone (45 mL) and water (9 mL) and AgNO3 (3.22 g, 16.3 mmol) were added. The flask was covered with aluminum foil to avoid decomposition of the AgNU3. The mixture was stirred at RT overnight. After filtration of the mixture and evaporation of the solvent, the residue was partitioned between EA (700 mL) and sat. NaHCC>3 solution (350 mL). The organic layer was washed with water (1 x 350 mL) and sat. NaCl solution (1 x 350 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with n-hexane/EA 9:1) to give the title compound. GC/MS (m/z): 198 |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 29% | With triethylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; at 60℃; for 3h; | To a solution of <strong>[74733-30-5]methyl 4-(bromomethyl)-3-chlorobenzoate</strong> (10 g, 37.95 mmol) in MeOH (300 mL) was added TEA (4.2 mL, 30.36 mmol) and Pd(dppf)Cl2 (2.8 g, 3.8 mmol). The reaction was heated under 0.4 MPa CO pressure at 60C for 3 h, filtered and concentrated. The residue was purified by Combi-Flash (120 g silica gel, start PE / EA = 10 : 0 to 5 : 1 by gradient, 60 mL/min, 60 min, 3.6 L total solvent volume) to afford product as a white solid (2.7 g, 29%). MS (ESI): m/z 243.0 [M+l]+. |
[ 74733-30-5 ]
[ 603-35-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In toluene; at 70℃; for 6h; | The brominated intermediate from above (3.20 g, 12.17 mmol) was dissolved in toluene (100 mL) and triphenylphosphine (6.50 g, 12.17 mmol) was added. The reaction mixture was heated at 70 C for 6h. Precipitation was observed right away. On completion as monitored by TLC the reaction mixture was cooled to room temperature and diluted with toluene (100 mL). The precipitate was filtered, washed with hexanes and air dried to give 4.68 g of (2-chloro-4-(methoxycarbonyl)benzyl)triphenylphosphonium bromide as a white solid. ES+ (M+H)+ 445.1. | |
| 4.68 g | In toluene; at 70℃; for 6h; | The brominated intermediate from above (3.20 g, 12.17 mmol) was dissolved in toluene (100 mL) and triphenylphosphine (6.50 g, 12.17 mmol) was added. The reaction mixture was heated at 70 C. for 6 h. Precipitation was observed right away. On completion as monitored by TLC the reaction mixture was cooled to room temperature and diluted with toluene (100 mL). The precipitate was filtered, washed with hexanes and air dried to give 4.68 g of (2-chloro-4-(methoxycarbonyl)benzyl)triphenylphosphonium bromide as a white solid. ES+(M+H)+445.1. |

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