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Structure of 13473-01-3 * Storage: {[proInfo.prStorage]}
* 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.
a. 5-Chloro-2-methoxypyridine Sodium hydride (60percent in mineral oil, 5.50 g, 115 mmol, 2 eq) was added portionwise to dry methanol (distilled from Mg, 25 mL) under a nitrogen atmosphere. To this solution was added 2,5-dichloropyridine (10.0 g, 68 mmol). After refluxing the resulting solution for 18 h, the reaction was cooled and treated with excess solid potassium bicarbonate. The reaction was filtered and concentrated to 50percent of its original volume upon which the solution solidified. The solids were washed with hexane and combined washes were concentrated to an oil. The title compound was purified by reduced pressure distillation (102° C., 2400 pascal) to yield 6.30 g (65percent) of a colorless oil. MS (CI, CH4) m/z 144 (M+,100), 146 (44), 172 (M+28,19), 124 (9).
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1, 2000, # 8, p. 1245 - 1249
[2] Patent: US5512575, 1996, A,
With dmap; 1,1'-bis-(diphenylphosphino)ferrocene; nickel(II) chloride hexahydrate; zinc In acetonitrile at 80℃; for 3 h; Inert atmosphere; Sealed tube
General procedure: Under argon protection, NiCl2·6H2O (0.05mmo 1,11.9mg), dppf (0.06mmol, 33.3mg), Zn (0·2mmol, 13.0mg), DMAP (1.0mmol, 122.2mg), Zn(CN)2 (0.8mmol) , 93.9mg), p-Chloroanisole (1.0 mmol, 140.6 mg) and acetonitrile (5.0 mL) were sequentially added in a 25.0 mL sealed tube, then directly put it into the oil bath at 60 °C, and heating was stopped after 6h, and cooled to room temperature, the reaction solution was directly filtered through a short silica gel column, washed with dichloromethane, concentrated and purified by silica gel column chromatography( given that the product is most easily pulled out, in order to avoid loss of sample mix, unless otherwise noted, both are wet method). Eluent: petroleum ether / ethyl acetate = 20:1, the product was 117.2 mg as a white solid, yield 88percent, and 1H NMR purity was greater than 98percent.
Reference：
[1] Organic Letters, 2017, vol. 19, # 8, p. 2118 - 2121
[2] Patent: CN108623495, 2018, A, . Location in patent: Paragraph 0043; 0045; 0178-0180
PREPARATION 13; (5-Chloro-2-methoxypyridin-3-yl)boronic acid a) 3-Bromo-5-chloro-2-methoxypyridineA solution of bromine (1.5 mL, 29.28 mmol) in glacial acetic acid (7 mL) was slowly added to a mixture of 5-chloro-2-methoxypyridine (2.1 g, 14.63 mmol) and sodium acetate (1.2 g, 14.63 mmol) in glacial acetic acid (7 mL) and the resulting mixture was stirred at 80 °C for 6 hours. The reaction was allowed to cool down to ambient temperature and then diethyl ether and water were added. The organic layer was separated, washed with a 1N aqueous solution of sodium hydroxide and a 4percent aqueous solution of sodium bisulphite, dried over magnesium sulphate and the solvent removed under reduced pressure. The residue was purified by flash chromatography (100percent hexanes) to give the title compound (2.1 g, 64percent) as a white solid.1H-NMR δ (300 MHz, CDCI3): 3.99 (s, 3H), 7.81 (d, 1H), 8.05 (d, 1H).
64%
Stage #1: at 80℃; for 6 h; Stage #2: With sodium hydroxide In diethyl ether; water
PREPARATION 13; (5-Chloro-2-methoxypyridin-3-yl)boronic acid a) 3-Bromo-5-chloro-2-methoxypyridine A solution of bromine (1.5 mL, 29.28 mmol) in glacial acetic acid (7 mL) was slowly added to a mixture of 5-chloro-2-methoxypyridine (2.1 g, 14.63 mmol) and sodium acetate (1.2 g, 14.63 mmol) in glacial acetic acid (7 mL) and the resulting mixture was stirred at 80 C for 6 hours. The reaction was allowed to cool down to room temperature and then diethyl ether and water were added. The organic layer was separated, washed with a 1 N aqueous solution of sodium hydroxide and a 4percent aqueous solution of sodium bisulphite, dried over magnesium sulphate and the solvent removed under reduced pressure. The residue was purified by flash chromatography (100percent hexanes) to give the title compound (2.1 g, 64percent) as a white solid. 1H-NMR δ (300 MHz, CDCl3): 3.99 (s, 3H), 7.81 (d, 1H), 8.05 (d, 1H).
Reference：
[1] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 1583 - 1592
[2] Journal of Medicinal Chemistry, 1986, vol. 29, # 9, p. 1590 - 1595
[3] Patent: WO2012/69202, 2012, A1, . Location in patent: Page/Page column 53
[4] Patent: EP2463289, 2012, A1, . Location in patent: Page/Page column 21
[5] Patent: US5512575, 1996, A,
[6] Patent: US4588733, 1986, A,
14
[ 13473-01-3 ]
[ 5419-55-6 ]
[ 475275-69-5 ]
Yield
Reaction Conditions
Operation in experiment
10.44 g
With lithium hexamethyldisilazane In tetrahydrofuran; n-heptane; ethylbenzene at -78 - 20℃;
General procedure: General Method 1A: Preparation of a boronic acid At-78C, LDA (2 molar in THF/heptane/ethylbenzene) was added to a solution of theappropriate pyridine derivative in THF (3 ml/mmol), the mixture was stirred for2-4 h and triisopropyl borate was then added quickly. The reaction mixture wasmaintained at -78 C for a further 2-3 h and then slowly thawed to RT overnight.After addition of water, the THF was removed under reduced pressure and theaqueous phase was extracted twice with ethyl acetate The aqueous phase wasacidified with 2M hydrochloric acid, generally resulting in formation of aprecipitate which was filtered off, washed with water and dried. The aqueousphase was extracted three times with ethyl acetate. The combined organic phaseswere dried (sodium sulphate), filtered and concentrated under reduced pressure.10.0 g (69.65 mmol) of 5-chloro-2-methoxypyridine werereacted according to General Method 1A.The desired product precipitated on acidification with hydrochloric acid (2N).Yield: 10.44 g (purity 91percent, 73percent of theory)
16 g
Stage #1: With n-butyllithium In tetrahydrofuran at -30℃; for 0.5 h; Inert atmosphere Stage #2: With 1,4,7,10-tetramethyl-1,4, 7,10-tetraazacyclododecane In tetrahydrofuran at -30 - 20℃; for 4 h; Stage #3: With hydrogenchloride In tetrahydrofuran; water for 1 h;
Under a nitrogen atmosphere, 300 g of anhydrous tetrahydrofuran was added to the reaction flask, stirring was continued, 17 g of 5-chloro-2-methoxypyridine was added and cooled to -30C.A solution of 70 mL of 2.0 M of n-BuLi was slowly added dropwise, and after stirring for 30 minutes, 1,3 g of 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane was slowly added dropwise.After 2 hours of incubation, 41 mL of triisopropyl borate was slowly added dropwise at -30 ° C, stirred for 1 hr, slowly raised to room temperature and stirred for 1 hour.And 400 g of concentrated hydrochloric acid was added thereto, followed by stirring for 1 hour to carry out a hydrolysis reaction.The layers were allowed to stand, and the organic layer was washed three times with water (3 x 100 g).The aqueous layers were combined and the aqueous layer was extracted once with 100 ml of petroleum ether. The combined organic layers were dried over 50 g of anhydrous sodium sulfate and filtered.The filtrate was concentrated to dryness to give 6-chloro-2-methoxy-4-pyridine boronic acid 16 g,
Reference：
[1] Patent: KR2015/137095, 2015, A, . Location in patent: Paragraph 0706; 0707; 1293-1296
[2] Patent: US2016/272637, 2016, A1, . Location in patent: Paragraph 0673; 0674; 0675; 0676
[3] Patent: CN102718785, 2016, B, . Location in patent: Paragraph 0036; 0037
15
[ 13473-01-3 ]
[ 475275-69-5 ]
Reference：
[1] Journal of Organic Chemistry, 2002, vol. 67, # 21, p. 7541 - 7543
[2] Patent: US2016/52884, 2016, A1, . Location in patent: Paragraph 0548; 0925-0928
16
[ 13473-01-3 ]
[ 121-43-7 ]
[ 475275-69-5 ]
Yield
Reaction Conditions
Operation in experiment
16 g
Stage #1: With n-butyllithium In tetrahydrofuran at -30℃; for 0.5 h; Inert atmosphere Stage #2: With N,N',N''-trimethyl-1,4,7-triazacyclononane In tetrahydrofuran at -30 - 20℃; for 4 h; Stage #3: With hydrogenchloride In tetrahydrofuran; water for 1 h;
Under a nitrogen atmosphere, 300 g of anhydrous tetrahydrofuran was added to the reaction flask, stirring was continued, 17 g of 5-chloro-2-methoxypyridine was added and cooled to -30C.Sulfur was added dropwise to 70 mL of 2.0 M of n-BuLi. After stirring for 30 minutes, 26 g of 1,4,7-trimethyl-1,4,7-triazacyclononane was slowly added dropwise.After incubation for 2 hours, 26 mL of trimethyl borate was slowly added dropwise at -30 ° C, stirred for 1 hr, slowly rose to room temperature and stirred for 1 hour.And 400 g of concentrated hydrochloric acid was added thereto, followed by stirring for 1 hour to carry out a hydrolysis reaction.The layers were allowed to stand, and the organic layer was washed three times with water (3 x 100 g).The aqueous layers were combined and the aqueous layer was extracted once with 100 ml of petroleum ether. The combined organic layers were dried over 50 g of anhydrous sodium sulfate and filtered.The filtrate was concentrated to dryness to give 16 g of product 5-chloro-2-methoxy-4-pyridine boronic acid.
A solution of the formula A-2 (50 g), sodium methoxide in isopropanol (30%, 150 g) was placed in a reaction vessel, and the reaction mixture was stirred and heated to about 70 C, and stirring was continued for 20 hours. After the reaction mixture was cooled to room temperature, the solvent was removed, ethyl acetate and water were added to extract, and the organic phase was dried, filtered, and the solvent was evaporated, and purified by distillation under reduced pressure to give the compound of formula B-2 (34 g, yield 70%).
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 20℃; for 48h;
To a stirred solution of compound <strong>[13473-01-3]5-chloro-2-methoxypyridine</strong> (40g, 275.86mmol, 1 eq) in DCM (300ml) was added m-CPBA (142.3g, 827.58mmol, 3eq) at RT and then the reaction continued at RT for 48h. The reaction mixture was filtered and the filtrate was concentrated to obtain a crude mixture. The crude mixture was purified by column chromatography (100- 200mesh) using 10-100% EtOAc in petroleum ether as an eluent to afford compound 2 (33g, 74.20%) as off-white solid; LCMS [M+H]+ 160.
The 4-amino-<strong>[13473-01-3]5-chloro-2-methoxypyridine</strong> used as a starting material were prepared as follows:- Hydrogen peroxide (30% aqueous solution; 72 ml) was added dropwise to a stirred sample of acetic anhydride (58 ml) that had been cooled to 0 C. Trifluoroacetic anhydride (15 ml) was added dropwise to the resultant solution that was still cooled to 0 C. The mixture so obtained was stirred at 0 C for 1 hour. A solid sample of <strong>[13473-01-3]5-chloro-2-methoxypyridine</strong> (T. M. Bargar et AL., J. HETEROCYCLIC CHEM., 1985,22, 1583; 13 g) was added and the resultant mixture was stirred at ambient temperature for 12 hours and then heated to 80 C for 4 hours. After cooling, the reaction mixture was concentrated under vacuum and diluted with diethyl ether. Solid potassium carbonate and the minimum of water were added portionwise until the pH of the solution was basic. The organic layer was dried over magnesium sulphate and evaporated. The material so obtained was recrystallised from ethyl acetate. There was thus obtained <strong>[13473-01-3]5-chloro-2-methoxypyridine</strong> N-oxide as white crystals (7.5 g); NMR Spectrum: (CDC13) 4.08 (s, 3H), 6.84 (d, 1H), 7.27 (m, 1H), 8.31 (d, 1H)
EXAMPLE 1 To a stirred suspension of 14.8 g of 2,5-dichloropyridine in 50 ml of methanol was added 30 ml of a 25% solution of sodium methoxide in methanol and the mixture was heated to reflux under nitrogen. After 24 hours, another 30 ml of the sodium methoxide solution was added and reflux was continued for a total of 68 hours. The sodium chloride which precipitated was removed by filtration and the filtrate was concentrated at atmospheric pressure to about 1/4 the original volume and partitioned between ether and water. The aqueous layer was extracted with ether and the combined ether layers were washed with saturated sodium chloride solution, dried over potassium carbonate and concentrated at atmospheric pressure to a pale brown oil. This residue was distilled to give 5-chloro-2-methoxypyridine as a colorless liquid boiling at about 82-84 C. at 20 torr. When the above procedure was repeated using 2,5-dibromomopyridine, the product obtained was 5-bromo-2-methoxypyridine boiling at about 99-101 C. at 28 torr.
A mixture of 10 g of <strong>[13473-01-3]5-chloro-2-methoxypyridine</strong> and 220 mL of tetrahydrofuran is cooled to -78 C., followed by gradual addition of a freshly prepared solution of 14.1 mL of 2,2,6,6-tetramethylpiperidine in 50 mL of tetrahydrofuran and 36.4 mL of 2.3N n-butyllithium in hexane. After stirring for 4 hours at -78 C., 17.3 g of trimethyltin chloride dissolved in 30 mL of tetrahydrofuran are added to the reaction mixture. The reaction mixture is stirred at room temperature for 18 hours and then treated with 200 mL of water and 200 mL of aqueous 10% ammonium chloride solution and extracted with 500 ml and then 200 mL of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a column of silica, eluting with dichloromethane, to give 17.7 g of 5-chloro-2-methoxy-4-(trimethylstannyl)pyridine 156 in the form of a colourless oil.UPLC-MS-DAD-ELSD: Rt (min)=1.24; [M+H]+: m/z 308.1H NMR (400 MHz, DMSO-d6) delta ppm: 0.16 (t, J=29.6 Hz, 9 H) 3.62 (s, 3 H) 6.61 (t, J=20.5 Hz, 1 H) 7.90 (t, J=8.3 Hz, 1 H).
A mixture of 10 g of <strong>[13473-01-3]5-chloro-2-methoxypyridine</strong> and 220 ml of tetrahydrofuran is cooled to -78 C., followed by gradual addition of a solution freshly prepared from 14.1 ml of 2,2,6,6-tetramethylpiperidine in 50 ml of tetrahydrofuran and 36.4 ml of 2.3 N n-butyllithium in hexane. After stirring for 4 hours at -78 C., 17.3 g of trimethyltin chloride dissolved in 30 ml of tetrahydrofuran are added to the reaction mixture. The reaction mixture is stirred at room temperature for 18 hours and then treated with 200 ml of water and 200 ml of aqueous 10% ammonium chloride solution and extracted with 500 ml and then 200 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a column of silica, eluting with dichloromethane to give 17.7 g of 5-chloro-2-methoxy-4-(trimethylstannyl)pyridine A2 in the form of a colourless oil.UPLC-MS-DAD-ELSD: Tr (min)=1.24; [M+H]+: m/z 308; purity: 98%1H NMR (400 MHz, DMSO-d6): ppm 0.16 (t, J=29.6 Hz, 9H) 3.62 (s, 3H) 6.61 (t, J=20.5 Hz, 1H) 7.90 (t, J=8.3 Hz, 1H)
(5-chloro-2-methoxypyridin-4-yl)boric acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Preparation Example 27 n-Butyl lithium (1.55M hexane solution, 10 mL) was added at -78C to a mixture of diisopropylamine (1.4 g) and THF (20 mL), followed by stirring at the same temperature for 30 minutes. A mixture of <strong>[13473-01-3]5-chloro-2-methoxypyridine</strong> (1 g) and THF (5 mL) was added dropwise to the reaction mixture at -78C, followed by stirring at the same temperature for one hour. A mixture of triisopropyl borate (2.62 g) and THF (5 mL) was further added to the reaction mixture at the same temperature, followed by warming the reaction mixture to room temperature and stirring for 2 days. The reaction mixture was diluted with water and a 1M aqueous sodium hydroxide solution was added thereto, followed by extraction with ethyl acetate. The resulting aqueous layer was neutralized with 1M hydrochloric acid and extracted with ethyl acetate. The resulting organic layer was washed with water, dried and concentrated under reduced pressure to obtain (5-chloro-2-methoxypyridin-4-yl)boric acid (1.28 g).
potassium (phthalimidomethyl)trifluoroborate[ No CAS ]
[ 169045-08-3 ]
Yield
Reaction Conditions
Operation in experiment
35%
With dichloro bis(acetonitrile) palladium(II); potassium carbonate; XPhos; In water; tert-butyl alcohol; at 100℃; for 15h;Inert atmosphere;
General procedure for the cross-coupling reaction: In a microwave vial equipped with a stirring bar were successively introduced potassium phthalimidomethyltrifluoroborate (3a) (80.1 mg, 0.3 mmol), potassium carbonate (104 mg, 0.75 mmol), Pd(MeCN)2Cl2 (4.9 mg, 7.5 mol %), and X-Phos (17.9 mg, 15 mol %). The vial was capped and put under inert atmosphere (3 x vacuum/N2 cycles). The electrophile was then introduced using a microsyringe (0.25 mmol, 1.0 equiv) followed by 0.8 mL of degassed t-BuOH and 0.2 mL of degassed distilled water. The resulting mixture was then placed in an oil bath or an IKA-RCT hotplate-magnetic stirrer system preheated at 100 oC and stirred at this temperature for 542 h (reactions followed by TLC). After cooling to room temperature, the vial was uncapped and the reaction mixture was diluted with dichloromethane (5 mL) and water (5 mL). The aqueous layer was extracted with dichloromethane (2 x 15 mL). Organic layers were combined, washed with brine solution and dried over MgSO4, and the solvent was removed under vacuum to yield the crude product. The crude product was purified by flash column chromatography on silica gel using ethyl acetate/hexane as the eluent.
With bis(1-glycyl-3-methyl imidazolium chloride)palladium(II); triethylamine; at 25℃; for 10h;Ionic liquid; Green chemistry;Catalytic behavior;
General procedure: In a conical flask (50mL), a mixture of aryl halide (1 mmol), phenyl boronic acid (1.2 mmol),triethylamine (1 mmol), [Aemim]Br (1ml) and [Gmim]Cl-Pd (II) (0.1mol%, 5 mg)was added and stirred at 25OC for a period as indicated in Table 5(The reaction was monitored by HPLC and TLC). The resulting heterogeneousmixture was extracted with ethyl acetate or diethyl ether (3x 5 mL). Theorganic phase was separated and dried over anhydrous Na2SO4and evaporated. Evaporation of the solvent gave the crud product residue whichwas further purified by flash chromatography using n-hexane/EtOAc to give thedesired coupling product in 82-94% isolated yields.
With dichloro bis(acetonitrile) palladium(II); potassium carbonate; XPhos; In water; tert-butyl alcohol; at 100℃; for 16h;Inert atmosphere;
General procedure: In a microwave vial equipped with a stirring bar, potassium N-methyltrifluoroborate isoindolin-1-one (6) (80.1 mg, 0.316 mmol), potassium carbonate (104 mg, 0.752 mmol), Pd(MeCN)2Cl2 (4.9 mg, 7.5 mol%), and XPhos (17.9 mg, 15.0 mol%) were successively introduced. The vial was capped and put under inert atmosphere (3 x vacuum/N2 cycles). The electrophile was then introduced using a microsyringe (0.25 mmol, 1.0 equiv.) followed by 0.8 mL of degassed t-BuOH and 0.2 mL of degassed distilled water. The resulting mixture was then placed in an oil bath or a hotplate-magnetic stirrer system preheated at 100 C and stirred at this temperature overnight (reactions followed by thin-layer chromatography, TLC). After cooling to room temperature, the vial was uncapped and the reaction mixture was diluted with dichloromethane (DCM) (5 mL) and water (5 mL). The aqueous layer was extracted with dichloromethane (3 x 15 mL). Organic layers were combined, washed with brine solution, and dried over Na2SO4, and the solvent was removed under vacuum to yield the crude product. The crude product was purified by flash column chromatography on silica gel using 30% ethyl acetate/hexane as the eluent.
General procedure: To an oven dried glass vessel capable of being sealed with a Teflon cap (for microwave vials) was added XPhos-Pd-G2 (11.8mg, 15mumol), XPhos (14.3mg, 30mumol), B2(OH)4 (203mg, 2.25mmol), KOAc (441mg, 4.5mmol), and halide (only if a solid). The vessel was sealed, evacuated, and filled with an inert gas (4×). EtOH (15mL, degassed) was added via syringe followed by the addition of ethylene glycol (280mg, 250muL, 4.5mmol) and the halide (1.5mmol) in a similar manner (if applicable). The reaction was heated to the specified temperature until the starting material was consumed (as monitored by GC). The reaction was cooled, and a needle attached to a manifold under an inert atmosphere was inserted into the septum, and 3equiv of degassed K3PO4 (1M, 4.5mL, 4.5mmol) was added via syringe, and the reaction was allowed to sit for 5min. Then the second halide was added in a similar manner (as a solution in 500muL of degassed EtOH or THF if a solid). The manifold needle was removed, and the reaction was heated to the specified temperature for 24h. The reaction was cooled to rt and filtered through a very thin pad of Celite, eluting with 5×10mL of EtOAc, and then concentrated. The crude reaction was dissolved in EtOAc (10mL), transferred to a separatory funnel, and then saturated NaHCO3 (10mL) was added. The aqueous layer was extracted with EtOAc (3×5mL). The combined organics were dried (Na2SO4), filtered, and concentrated. The desired compound was purified by silica gel column chromatography, eluting with EtOAc/hexane.
General procedure: To an oven dried glass vessel capable of being sealed with a Teflon cap (for microwave vials) was added XPhos-Pd-G2 (11.8mg, 15mumol), XPhos (14.3mg, 30mumol), B2(OH)4 (203mg, 2.25mmol), KOAc (441mg, 4.5mmol), and halide (only if a solid). The vessel was sealed, evacuated, and filled with an inert gas (4×). EtOH (15mL, degassed) was added via syringe followed by the addition of ethylene glycol (280mg, 250muL, 4.5mmol) and the halide (1.5mmol) in a similar manner (if applicable). The reaction was heated to the specified temperature until the starting material was consumed (as monitored by GC). The reaction was cooled, and a needle attached to a manifold under an inert atmosphere was inserted into the septum, and 3equiv of degassed K3PO4 (1M, 4.5mL, 4.5mmol) was added via syringe, and the reaction was allowed to sit for 5min. Then the second halide was added in a similar manner (as a solution in 500muL of degassed EtOH or THF if a solid). The manifold needle was removed, and the reaction was heated to the specified temperature for 24h. The reaction was cooled to rt and filtered through a very thin pad of Celite, eluting with 5×10mL of EtOAc, and then concentrated. The crude reaction was dissolved in EtOAc (10mL), transferred to a separatory funnel, and then saturated NaHCO3 (10mL) was added. The aqueous layer was extracted with EtOAc (3×5mL). The combined organics were dried (Na2SO4), filtered, and concentrated. The desired compound was purified by silica gel column chromatography, eluting with EtOAc/hexane.
potassium 6-methoxypyridin-3-yltrifluoroborate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88%
General procedure: an oven dried glass vessel capable of being sealed with a Teflon cap (for microwave vials) was added XPhos-Pd-G2 (5.89mg, 7.5mumol), XPhos (7.14mg, 15mumol), B2(OH)4 (203mg, 2.25mmol), KOAc (441mg, 4.5mmol), and halide (only if a solid). The vessel was sealed, evacuated, and filled with an inert gas (4×). EtOH (15mL, degassed) was added via syringe followed by the addition of ethylene glycol (280mg, 250muL, 4.5mmol) and the halide (1.5mmol) in a similar manner (if applicable). The reaction was heated to the specified temperature until the starting material was consumed (monitored by GC). The reaction was cooled to rt and filtered through a very thin pad of Celite and decolorizing carbon (eluting with 5×10mL of EtOAc) and concentrated. The crude reaction was dissolved in EtOAc (10mL), transferred to a separatory funnel, and then H2O (10mL) was added. The layers were separated, and the organic layer was washed with brine (5mL). The combined aqueous layers were extracted with EtOAc (3×5mL) dried (Na2SO4), filtered, and concentrated. MeOH (?15mL) was added to concentrated crude reaction mixture, which was cooled to 0C. To this reaction mixture, KHF2 (1mL of 4.5M soln, 4.5equiv) was added. The reaction was stirred at 0C for 10min before removing the bath and allowing the reaction mixture to stir for 20min (or until conversion to trifluoroborate is complete as observed by 11B). The resulting mixture was concentrated and then lyophilized overnight to remove any traces of H2O. The compound was purified with continuous Soxhlet extraction (8h or by complete disappearance of RBF3K in the thimble as determined by 11B NMR). The collected solvent was concentrated until a minimum amount of acetone (?3mL) remained. The addition of Et2O (?25mL) led to the precipitation of the desired product.
With dmap; 1,1'-bis-(diphenylphosphino)ferrocene; nickel(II) chloride hexahydrate; zinc; In acetonitrile; at 80℃; for 3h;Inert atmosphere; Sealed tube;
General procedure: Under argon protection, NiCl2·6H2O (0.05mmo 1,11.9mg), dppf (0.06mmol, 33.3mg), Zn (0·2mmol, 13.0mg), DMAP (1.0mmol, 122.2mg), Zn(CN)2 (0.8mmol) , 93.9mg), p-Chloroanisole (1.0 mmol, 140.6 mg) and acetonitrile (5.0 mL) were sequentially added in a 25.0 mL sealed tube, then directly put it into the oil bath at 60 C, and heating was stopped after 6h, and cooled to room temperature, the reaction solution was directly filtered through a short silica gel column, washed with dichloromethane, concentrated and purified by silica gel column chromatography( given that the product is most easily pulled out, in order to avoid loss of sample mix, unless otherwise noted, both are wet method). Eluent: petroleum ether / ethyl acetate = 20:1, the product was 117.2 mg as a white solid, yield 88%, and 1H NMR purity was greater than 98%.
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