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Chemical Structure| 176022-47-2 Chemical Structure| 176022-47-2
Chemical Structure| 176022-47-2

(S)-(4-Chlorophenyl)(pyridin-2-yl)methanol

CAS No.: 176022-47-2

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Cat. No.: A252693 Purity: 97%

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Product Details of [ 176022-47-2 ]

CAS No. :176022-47-2
Formula : C12H10ClNO
M.W : 219.67
SMILES Code : O[C@@H](C1=CC=C(Cl)C=C1)C2=NC=CC=C2
MDL No. :MFCD14636162
InChI Key :ZFUPOFQRQNJDNS-LBPRGKRZSA-N
Pubchem ID :11020392

Safety of [ 176022-47-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Application In Synthesis of [ 176022-47-2 ]

* 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.

  • Downstream synthetic route of [ 176022-47-2 ]

[ 176022-47-2 ] Synthesis Path-Downstream   1~28

  • 1
  • [ 17624-36-1 ]
  • [ 104-88-1 ]
  • [ 176022-47-2 ]
  • [ 112966-26-4 ]
  • 2
  • [ 6318-51-0 ]
  • [ 176022-47-2 ]
  • [ 112966-26-4 ]
YieldReaction ConditionsOperation in experiment
With Kluyveromyces polysporus alcohol dehydrogenase S237R mutant; isopropyl alcohol; NADPH; In aq. phosphate buffer; at 30℃;pH 7.0;Enzymatic reaction;Kinetics; Catalytic behavior; General procedure: Bioconversion was conducted with 20 mM 1a-10a,20 U·mL-1KpADH variants, 40 mM isopropanol in PBS buffer (pH 7.0,100 mM) in total volume of 2 mL at 30 C and 180 rpm overnight. Then,1 mL of the reaction mixture was withdrawn and extracted with ethylacetate. The organic phase was isolated by centrifugation and driedover anhydrous MgSO4. The conversion rate and enantioselectivity ofthe products were analyzed as described in supporting information.
With Kluyveromyces polysporus alcohol dehydrogenase E214 G/S237C mutant variant; NADPH; In aq. phosphate buffer; at 30℃;pH 7.0;Enzymatic reaction;Kinetics; General procedure: Six variants with significantly improved activity were selected to test their stereoselectivity and conversion rate. Bioconversion was conducted with 20mM 1a-9a, 20UmL-1 KpADH or variants in PBS buffer (pH 7.0, 100mM) in total volume of 2mL at 30C and 180rpm overnight. Then, 1mL of the reaction mixture was withdrawn and extracted with equal volume of ethyl acetate. The organic phase was isolated by centrifugation at 12000×g for 2min, and dried over anhydrous MgSO4. The conversion rate and stereoselectivity of the products were determined using the Agilent 1100 equipped with a Chiralcel OB-H column or a Chiralcel OD-H column (0.46mm×250mm×5μm, Diacel, Japan). Detailed conditions for stereoselectivity analysis and the retention times of (R)- and (S)-alcohols could be found in Table S3 [28].
  • 3
  • Trifluoro-methanesulfonate1-allyl-2-[(S)-(4-chloro-phenyl)-hydroxy-methyl]-pyridinium; [ No CAS ]
  • [ 176022-47-2 ]
  • 4
  • [ 176022-47-2 ]
  • [ 2675-89-0 ]
  • [ 182009-51-4 ]
  • 6
  • [ 6318-51-0 ]
  • [ 176022-47-2 ]
YieldReaction ConditionsOperation in experiment
99.7% With (R,R)-DIOPRuCl2(R)-Me-BIMAH; potassium tert-butylate; hydrogen; In toluene; at 35℃; under 26601.8 Torr; for 4h;Autoclave; In a 5L autoclave, under the condition of argon, 400 g of (4-chlorophenyl)(pyridin-2-yl)methanone was added from the feed inlet; 3 L of toluene was added; Bubble out of gas, continuous bubbling 30min; degassing is complete. Under an argon atmosphere, 100 mg of catalyst (R,R)-DIOPRuCl2(R)-Me-BIMAH was added from the feed port, and finally 6 g of potassium tert-butoxide was added; after the addition was completed, the feed port was quickly closed tightly. Replacing argon with hydrogen gas and slowly introducing hydrogen gas to 35 atm, and then closing the inflation valve and closing the hydrogen channel; finally stirring, maintaining the reaction at 35 C.; after the start of stirring, the pressure dropped. Observe the changes in pressure, after 4h, the pressure no longer changes, sampling for GC analysis,The conversion rate was 99.7% and the ee value was 98.2%.
96% With bis(1,5-cyclooctadiene)diiridium(I) dichloride; N-((1R,2R)-2-(((R)-1-(2-(diphenylphosphanyl)ferrocenyl)ethyl)amino)cyclohexyl)-2,4,6-trimethylbenzenesulfonamide; hydrogen; lithium tert-butoxide; In methanol; at 40℃; under 22502.3 Torr; for 12h;Autoclave;Catalytic behavior; (1) The chiral ligand L2 (17.3 mg, 0.025 mmol), metal complex [Ir(COD)Cl] 2 (8.0 g,0.012 mmol) was added to the reaction flask, methanol (1.5 mL) was added under an argon atmosphere, and the reaction was stirred at 25 C for 0.5 h to obtain a catalyst.(2) (4-Chlorophenyl)(pyridin-2-yl)methanone (52.2 g, 0.24 mol) was added to the autoclave, and the catalyst prepared in the step (1) was directly added, lithium t-butoxide (0.96 g). , 12mmol), methanol (100mL), charged with H2 (3.0MPa), reacted at 40 C for 12h, after the reaction is completed, the reaction solution is concentrated under reduced pressure to recover the organic solvent, then add appropriate amount of water, extracted with ethyl acetate, the liquid is The organic phase and the aqueous phase are dried and de-solubilized to obtain (S)-(4-chlorophenyl)(pyridin-2-yl)methanol (50.5 g,0.23 mol), yield: 96%, HPLC purity 98%, ee value 99.9%.The 1H NMR spectrum and the 13C NMR spectrum of (S)-(4-chlorophenyl)(pyridin-2-yl)methanol prepared in this example are shown in Fig. 1 and Fig. 2, respectively, from Fig. 1 and Fig. 2 The resulting (S)-(4-chlorophenyl)(pyridin-2-yl)methanol product can be determined. Racemic compound (4-chlorophenyl)(pyridin-2-yl)methanol and (S)-(4-chlorophenyl) prepared in Example 10The HPLC analysis spectra of the (pyridin-2-yl)methanol product are shown in Figures 3 and 4, respectively.Comparing Fig. 3 and Fig. 4, it can be seen that the two racemates of (4-chlorophenyl)(pyridin-2-yl)methanol have different peak times in the HPLC analysis spectrum.It was confirmed that the final preparation of Example 10 was (S)-(4-chlorophenyl)(pyridin-2-yl)methanol, and the product was highly pure.
  • 7
  • [ 873-77-8 ]
  • (+-)-2-hydroxy-1-phenyl-propan-1-one [ No CAS ]
  • [ 176022-47-2 ]
  • 8
  • [ 176022-47-2 ]
  • [ 5560-77-0 ]
  • 9
  • Trifluoro-methanesulfonate1-allyl-2-(4-chloro-benzoyl)-pyridinium; [ No CAS ]
  • [ 176022-47-2 ]
  • 10
  • [ 7677-24-9 ]
  • [ 104-88-1 ]
  • [ 74-86-2 ]
  • [ 176022-47-2 ]
  • 11
  • [ 106-39-8 ]
  • [ 176022-47-2 ]
  • 12
  • [ 176022-47-2 ]
  • (S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidin-1-yl]butyramide [ No CAS ]
  • 14
  • [ 176022-47-2 ]
  • (S)-(-)-2-((4-chlorophenyl)(piperidin-4-yloxy)methyl)pyridine [ No CAS ]
  • 15
  • 4-[4-bromopiperidinyl]butanamide [ No CAS ]
  • [ 176022-47-2 ]
  • (S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidin-1-yl]butyramide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With sodium hydride; In tetrahydrofuran; at 0 - 40℃; for 8h;Inert atmosphere; 109.8 g (0.5 mol) of (S) - (+) - (4-chlorophenyl) - (pyridin-2-yl) -methanol (Formula II) was dissolved in 1 L of tetrahydrofuran under nitrogen,Cooled to 0 ,22.3 g (0.56 mol) of sodium hydride in a mass fraction of 60% was added under stirring,Stir vigorously until no gas is generated.138.38 g (0.55 mol) of 4- [4-bromopiperidinyl] butanamide was added dropwise at 0 C,In dry tetrahydrofuran (100 mL)Heating to 40 C reaction 8h,Cooled to 0 ,Saturated aqueous ammonium chloride solution (500 mL) was added dropwise,Extraction with ethyl acetate (400 mL x 3)The ethyl acetate layer was concentrated to dryness under reduced pressure,Dried over anhydrous sodium sulfate for 2 hours,The product was 147 g,Yield 75%.
  • 16
  • [ 176022-47-2 ]
  • [ 180695-79-8 ]
  • (S)-N-tert-butoxycarbonyl-4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% The tetrahydrofuran in Example 1 was replaced by the same amount of N, N-dimethylformamide, and the other procedures were the same as in Example 1,Rate 88%. (S) - (4-chlorophenyl) (2-pyridyl) -methanol 21.9 g (0.1 mol) of the formula (II)Was dissolved in 160 mL of tetrahydrofuran,41 g (0.1 mol) of sodium hydride in a mass fraction of 60% was added portionwise with stirring,Stirring for 2 hours to no bubbles,The reaction was allowed to cool under ice-coolingA solution of 26.4 g (0.1 mol) of N-t-butoxycarbonyl-4-bromopiperidine was added dropwise,After completion of the dropwise addition, the reaction was gradually warmed to room temperature with stirring for 5 hours,The reaction solution was added to 200 mL of saturated ammonium chloride solution,Stirred for 30 minutes,The reaction solution was extracted twice with 300 mL of ethyl acetate,The organic phases were combined,Dried over anhydrous sodium sulfate for 2 hours,filter,The mother liquor was evaporated to dryness to give 34.3 g of product,The product was directly subjected to the next reaction without purification,Yield 85%.
  • 17
  • tert-butyl 4-chloropiperidine-1-carboxylate [ No CAS ]
  • [ 176022-47-2 ]
  • (S)-N-tert-butoxycarbonyl-4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% The N-tert-butoxycarbonyl-4-bromopiperidine in Example 1 was replaced by an equimolar amount of N-tert-butoxycarbonyl-4-chloropiperidineIt was run in the same manner as in Example 1, and the yield of the product was 82%. (S) - (4-chlorophenyl) (2-pyridyl) -methanol 21.9 g (0.1 mol) of the formula (II)Was dissolved in 160 mL of tetrahydrofuran,41 g (0.1 mol) of sodium hydride in a mass fraction of 60% was added portionwise with stirring,Stirring for 2 hours to no bubbles,The reaction was allowed to cool under ice-coolingA solution of 26.4 g (0.1 mol) of N-t-butoxycarbonyl-4-bromopiperidine was added dropwise,After completion of the dropwise addition, the reaction was gradually warmed to room temperature with stirring for 5 hours,The reaction solution was added to 200 mL of saturated ammonium chloride solution,Stirred for 30 minutes,The reaction solution was extracted twice with 300 mL of ethyl acetate,The organic phases were combined,Dried over anhydrous sodium sulfate for 2 hours,filter,The mother liquor was evaporated to dryness to give 34.3 g of product,The product was directly subjected to the next reaction without purification,Yield 85%.
  • 18
  • [ 176022-47-2 ]
  • [ 301673-14-3 ]
  • (S)-N-tert-butoxycarbonyl-4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% N-tert-butoxycarbonyl-4-bromopiperidine in Example 1 was replaced by an equimolar amount of N-t-butoxycarbonyl-4-iodopiperidine,The same operation as in Example 1 was followed except that the yield of the product was 84%. (S) - (4-chlorophenyl) (2-pyridyl) -methanol 21.9 g (0.1 mol) of the formula (II)Was dissolved in 160 mL of tetrahydrofuran,41 g (0.1 mol) of sodium hydride in a mass fraction of 60% was added portionwise with stirring,Stirring for 2 hours to no bubbles,The reaction was allowed to cool under ice-coolingA solution of 26.4 g (0.1 mol) of N-t-butoxycarbonyl-4-bromopiperidine was added dropwise,After completion of the dropwise addition, the reaction was gradually warmed to room temperature with stirring for 5 hours,The reaction solution was added to 200 mL of saturated ammonium chloride solution,Stirred for 30 minutes,The reaction solution was extracted twice with 300 mL of ethyl acetate,The organic phases were combined,Dried over anhydrous sodium sulfate for 2 hours,filter,The mother liquor was evaporated to dryness to give 34.3 g of product,The product was directly subjected to the next reaction without purification,Yield 85%.
  • 19
  • [ 176022-47-2 ]
  • [ 125602-71-3 ]
  • 20
  • [ 176022-47-2 ]
  • (R)-(-)-α-(4-chlorophenyl)-(2-pyridyl)methyl chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
92.3% With pyridine; thionyl chloride; In 5,5-dimethyl-1,3-cyclohexadiene; at 0 - 30℃; for 4h; 5 g (22.8 mM) of (S)-(+)-(4-chlorophenyl)-2-pyridylmethanol was added to 30 ml of xylene, to which 7.5 ml (11 mM) of pyridine was added followed by thionyl chloride 2 ml (25 mM) at 0 C drop it. After stirring for 2 hours, the temperature is slowly raised to 20 C, stirred further at 30 C for 2 hours, and then cooled again to 0-5 C. 30 ml of distilled water was carefully added to the mixture, and then 35 ml of concentrated ammonia water was slowly added thereto. After confirming that the mixture becomes strong alkali, the layers are separated, and the organic layer is washed with distilled water, saturated saline, and distilled water in 10 ml increments. The solution is dried with anhydrous magnesium sulfate for 10 minutes and filtered. The filtrate was distilled under reduced pressure to remove the xylene to obtain 0.5 g (92.3%) of the target compound.
  • 21
  • [ 176022-47-2 ]
  • (S)-(+)-4-[4-[(4-chlorophenyl)-(2-pyridyl)methoxy]piperidino]butanoic acid ethyl ester [ No CAS ]
  • 23
  • (S)-2-((4-chlorophenyl)(hydroxy)methyl)pyridine 1-oxide [ No CAS ]
  • [ 176022-47-2 ]
YieldReaction ConditionsOperation in experiment
93% With ammonium chloride; zinc; In tetrahydrofuran; water; at 35℃; for 12h; 0.23 g of (S) - (4-chlorophenyl) (2-pyridyl) methanol-N-oxide obtained in Example 3 was dissolved in 15 mLTetrahydrofuran, 0.6g of zinc powder, 15mL of 30% aqueous ammonium chloride, 35 reaction 12h, extracted with ethyl acetate, the organic phase Drying and removing the solvent gave 0.21 g of (S) - (4-chlorophenyl) (2-pyridyl) methanol as a white solid in 93% yield.The enantiomeric excess ee of (S) - (4-chlorophenyl) (2-pyridyl) methanol was 94%.
93% With hydroxylamine hydrochloride; zinc; In tetrahydrofuran; water; at 35℃; for 12h; 0.23 g of (S)-(4-chlorophenyl)(2-pyridyl)methanol-N-oxide prepared in Example 5 was dissolved in 15 mLIn tetrahydrofuran,Add 0.6g zinc powder,15mL of 30% aqueous solution of ammonium chloride,Reaction at 35C for 12hEthyl acetate extraction,The organic phase is dry and desolventizedObtained white solid (S)-(4-chlorophenyl) (2-pyridyl)methanol 0.21g, 93% yield,The product (S)-(4-chlorophenyl)(2-pyridyl)methanol was measured by HPLC for an enantiomeric excess ee of 98%.
  • 24
  • ethyl 4-(4-bromopiperidin-1-yl)butanoate [ No CAS ]
  • [ 176022-47-2 ]
  • (S)-(+)-4-[4-[(4-chlorophenyl)-(2-pyridyl)methoxy]piperidino]butanoic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydride; In tetrahydrofuran; mineral oil; at 0 - 40℃; for 8h;Inert atmosphere; 0.2 g of (S) - (4-chlorophenyl) (2-pyridyl) methanol obtained in Example 4 was dissolved in 5 mL of tetrahydrofuran,Add at 0 C in portions40mg 60% NaH, purged with nitrogen, stirred until no gas generated. Slowly add 0.28g Ethyl 4- (4-bromopiperidin-1-yl) butanoateOf anhydrous tetrahydrofuran solution, after the addition was complete, the temperature was raised to 40 reaction 8h, cooled to 0 , the dropwise addition of saturated chlorine Aqueous solution of ammonium, extracted with ethyl acetate, the organic phase is dried, and the solution is taken out to obtain 0.34 g of colorless and educt, the yield is 90%.
  • 25
  • ethyl 4-(4-bromopiperidin-1-yl)butanoate [ No CAS ]
  • [ 176022-47-2 ]
  • [ 98-11-3 ]
  • [ 125602-71-3 ]
  • 26
  • C12H10ClNO2 [ No CAS ]
  • [ 176022-47-2 ]
  • 27
  • [ 107-99-3 ]
  • [ 176022-47-2 ]
  • [ 5560-77-0 ]
YieldReaction ConditionsOperation in experiment
85% 0.44 g of <strong>[176022-47-2](S)-(4-chlorophenyl)(2-pyridyl)methanol</strong> prepared in Example 6 was dissolved in 5 mL of DMF.Add 0.1g sodium hydroxide,Stir for 30min;Then 0.24 g of 2-chloro-N,N-dimethylethylamine and 0.28 g of potassium carbonate were added,Heat to 90C, react for 10h,Cool to room temperatureDiluted with water,Extract three times with ethyl acetate,Concentrate to dryness,Recrystallization from petroleum ether and ethyl acetate gave 0.49 g of product.Yield 85%,The product S-carbethamine had an enantiomeric excess ee of 98% as determined by HPLC.
YieldReaction ConditionsOperation in experiment
99% With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C39H45FeN2O2PS; hydrogen; lithium tert-butoxide; In methanol; at 40℃; under 22502.3 Torr; for 12h;Autoclave; General procedure: 1) Chiral ligand I-2 (17.3 mg, 0.025 mmol),Metal complex [Ir(COD)Cl] 2 (8.0 g,0.012mmol),Add to the reaction flask,Add methanol (1.5 mL) under an argon atmosphere.The reaction was stirred at 25 C for 0.5 h.A catalyst is obtained.2) adding a phenyl(pyridin-2-yl)methanone derivative (0.24 mol) to the autoclave,Adding the catalyst prepared in step 1),Lithium tert-butoxide (12 mmol),Methanol (100mL),Filled with H2 (3.0MPa),Reaction at 40 C for 12 h,After the reaction,The reaction solution is concentrated under reduced pressure to recover an organic solvent.Add the right amount of water,Extracted with ethyl acetate,The liquid separation is organic and aqueous, andMachine phase is dry,Desolvent,Producing (S)-phenyl(pyridin-2-yl)methanol derivatives,The purity, yield and ee value of the product are shown in Table 1.
 

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