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CAS No. : | 180272-45-1 | MDL No. : | MFCD11858641 |
Formula : | C15H15N | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PRTRSEDVLBBFJZ-OAHLLOKOSA-N |
M.W : | 209.29 | Pubchem ID : | 1382088 |
Synonyms : |
|
Num. heavy atoms : | 16 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.2 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 70.27 |
TPSA : | 12.03 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | Yes |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.43 cm/s |
Log Po/w (iLOGP) : | 2.55 |
Log Po/w (XLOGP3) : | 3.02 |
Log Po/w (WLOGP) : | 2.22 |
Log Po/w (MLOGP) : | 3.2 |
Log Po/w (SILICOS-IT) : | 3.61 |
Consensus Log Po/w : | 2.92 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.53 |
Solubility : | 0.0619 mg/ml ; 0.000296 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.94 |
Solubility : | 0.242 mg/ml ; 0.00115 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -5.57 |
Solubility : | 0.000562 mg/ml ; 0.00000269 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.35 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
42% | With lithium aluminium tetrahydride In diethyl ether at 0℃; for 48h; | |
With lithium aluminium tetrahydride In diethyl ether at 0℃; for 48h; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With samarium diiodide; water; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; | |
68% | With ammonia; sodium In tetrahydrofuran at -78℃; for 0.75h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: (1R)-N-(8-menthyl)-1-phenyl-1,2,3,4-tetrahydroisoquinoline With 3 A molecular sieve; sodium acetate; pyridinium chlorochromate In dichloromethane at 20℃; for 48h; Stage #2: With potassium hydroxide In tetrahydrofuran Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With Li[AlH2(OCH3)2] In tetrahydrofuran at -50℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tetrahydroborate In ethanol at 20℃; for 60h; | ||
50 % ee | With hydrogen In tetrahydrofuran; 1,1-dichloroethane at 20 - 50℃; Inert atmosphere; | 1.B1 Example 1 Preparation of 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (II) Procedure B2: 0.0025 mmol [IrCOD)Cl]2 and 0.0055 mmol (S)-BINAP were weighted in a glass liner, placed in the hydrogenation reactor and then under inert atmosphere 3 mL of THF was added. The reaction was stirred at room temperature for 30 minutes and then a solution of 0.25 mmol of l-phenyl-3,4-dihydroisoquinoline was added. 2 mL of dichloroethane was added to solubilize l-phenyl-3,4-dihydroisoquinoline. The reaction was purged with hydrogen, heated to 50°C and hydrogen pressure topped up to 30 bar. After 3 hours the yield of the product was over 97% and the enantiomeric excess was 50 % (S). |
With 1,1'-bis-(diphenylphosphino)ferrocene; bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; iodine In dichloromethane at 20℃; for 24h; Inert atmosphere; Autoclave; optical yield given as %ee; enantioselective reaction; |
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; (R)-3,5-diMe-Synphos; hydrogen In 1,4-dioxane at 40℃; for 18h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
39 % ee | With formic acid; [RuCl(η6-benzene)(1R,2R)-N-(naphthalene-1-sulfonyl)-1,2-diphenylethylenediamine]; triethylamine In acetonitrile at 30℃; | General procedure for asymmetric transfer hydrogenation General procedure: The formic acid-triethylamine azeotropic mixture (218 μL; 6.3 eq of formic acid with respect to the imine) was charged into a round-bottom flask (10 mL), followed by the catalyst (0.01 eq) dissolved in acetonitrile (1 mL). The resulting mixture was stirred for 10 min to activate the catalyst. The imine (0.42 mmol) dissolved in acetonitrile (1 mL) was introduced at once and the mixture was stirred at 30 °C. The samples of the reaction mixture (60 μL) were collected at 10, 20, 30, 40, 50, 90, 120 and 180 min. (0014) Each sample was quenched by using saturated solution of Na2CO3 (1 mL) and extracted with diethyl ether (3 × 1 mL). Combined extracts were dried over anhydrous sodium sulfate and the solvent was stripped off in a stream of nitrogen. The dry sample was dissolved in acetonitrile (1 mL) and analyzed. |
63 % ee | With (2S,3R)-2-amino-3-hydroxybutanamide; streptavidin biotin-wild type; C42H64Cl4Ir2N6O4S2 In dimethyl sulfoxide at 30 - 50℃; for 18h; Overall yield = 96 %; enantioselective reaction; | |
16 % ee | With C42H64Cl4Ir2N6O4S2; D-Phenylalaninamide In dimethyl sulfoxide at 30 - 50℃; for 18.25h; Overall yield = 99 %; enantioselective reaction; | |
With [N-[(1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2,3,4,5,6-η)-1,3,5-trimethylbenzene]ruthenium; formic acid; triethylamine In acetonitrile for 1.16667h; Optical yield = 2 %ee; | 4.2. Standard hydrogenation procedure General procedure: The asymmetric transfer hydrogenation reactions were performed according to a previously reported procedure. A round bottom flask was equipped with a magnetic stirrer bar and was pre-heated on a water bath (30 C). Stock solutions of the substrates and catalyst were prepared. The amounts of reaction components were calculated in order to fulfill the following ratios: S/Cratio = 100, HCOOH/triethylamine ratio = 2.5, concentration = 7.0%(defined as: (mass of substrate + mass of catalyst + mass of formic acid + mass of triethylamine)/mass of solvent), hydrogenation mixture/substrate ratio = 8.83, total volume of reaction mixture = 2 mL (all ratios are molar). The components were transferred into the flask in the following order: acetonitrile, formic acid, triethylamine, solution of the catalyst. After five minutes, the calculated amount of the substrate solution containing 0.15 mmol of substrate was added into the reaction mixture. The samples were taken in defined time intervals. The samples were treated with a saturated solution of sodium carbonate (1 mL) and extracted three times with diethyl ether (3 1 mL). The extract was dried over sodium sulfate, filtered,and stripped in a stream of argon. The residue was dissolved in 600 μL of acetonitrile and analyzed via GC. After the addition of 20 μL triethylamine and 10 μL of ()-(R)-menthyl chloroformate,the enantioselectivity could be determined. | |
29 % ee | With [N-[(1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2,3,4,5,6-η)-1,3,5-trimethylbenzene]ruthenium; formic acid; triethylamine In isopropyl alcohol at 30℃; for 16h; Inert atmosphere; Overall yield = 90 %; enantioselective reaction; | |
11 % ee | With N-[(1S,2S)-1,2-diphenyl-2-(3-phenylpropylamino)ethyl]-4-methylbenzene sulfonamide ammonium chloride ruthenium; hydrogen; trifluoroacetic acid In methanol at 40℃; for 6h; Autoclave; Sealed tube; | |
24 % ee | With hydrogen In tetrahydrofuran; toluene at 30℃; for 17h; Autoclave; enantioselective reaction; | |
71 % ee | With (pentamethylcyclopentadienyl)IrCl[κ2(N,N')-(S,S)-p-toluenesulfonylNCHPhCHPhNH2]; hydrogen; trifluoroacetic acid In methanol for 6h; stereoselective reaction; | 23 General procedure: 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (1) (1.22mmol) was dissolved in methanol (14.0 mL), followed by adding thereto trifluoroacetic acid (93.42 μL, 1.22mmol), and the mixture was stirred for 5 minutes. The catalyst [RuCl2 (η6-p-cymene) (S, S)-(N-tosyl-1,2-diphenylethane-1,2-diamine)] (A) (0.0122 mol) was added to the mixture (molar substrate to catalyst ratio S / C = 100).The reaction system was sealed pressure reactor and replaced three times with hydrogen (3 × 5bar), then charged with hydrogen 15bar.After 6 hours of reaction, the reaction mixture was added saturated Na2CO3Mixed solution (2mL).The resulting solution was extracted twice with ether (3 × 2mL), the combined organic phases were dried over anhydrous Na2SO4 dried for 1 hour.The resulting ether solution was evaporated to dryness in air solvent vapor, GC analysis showed 1100% of the compound is converted to 6,7-dimethyl-1-methyl-1,2,3,4-tetrahydroisoquinoline, ee value 96%. Operation example 2 to 23 embodiment is substantially same as Example 1, except that different catalysts and starting materials, catalyst and feedstock, and conversion and ee values used are listed in Table 1. |
51 % ee | With D-glucose; BmGDH; imine reductase from Stackebrandtia nassauensis; NADP In aq. phosphate buffer; dimethyl sulfoxide at 30℃; for 12h; Enzymatic reaction; Overall yield = 81 %; Overall yield = 170 mg; enantioselective reaction; | |
86 % ee | With formic acid; (1,2,3,4,5-pentamethylcyclopentadienyl)Ir[κ2(N,N')-CH3C6H4SO2NCHPhCHPhNH]; phosphoric acid; triethylamine In isopropyl alcohol at 30℃; for 3h; Inert atmosphere; Schlenk technique; Overall yield = 90 %; Overall yield = 28.4 mg; enantioselective reaction; | |
30 % ee | With D-Glucose; NADPH at 30℃; for 24h; Enzymatic reaction; enantioselective reaction; | |
Multi-step reaction with 2 steps 1: borane-ammonia complex 2: LG-I-D11 / Resolution of racemate; Enzymatic reaction | ||
86 % ee | With N-Bromosuccinimide; bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl In 1,2-dichloro-ethane at 0℃; for 36h; Glovebox; Overall yield = 92 %; Overall yield = 57 mg; enantioselective reaction; | |
85 % ee | With Cp*Ir(biot-p-L)Cl; streptavidin S112A-N118P-K121A mutant In aq. buffer at 37℃; for 4h; Sealed tube; Enzymatic reaction; enantioselective reaction; | |
86 % ee | With Cp*Ir(biot-p-L)Cl; streptavidin S112A-N118P-K121A mutant In aq. buffer at 37℃; for 4h; Sealed tube; Enzymatic reaction; enantioselective reaction; | |
88 % ee | With N-Bromosuccinimide; chloro(1,5-cyclooctadiene)rhodium(I) dimer; hydrogen; sodium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,2-dichloro-ethane at 30℃; for 24h; Glovebox; enantioselective reaction; | 1 Example 1: Optimization of conditions In the glove box,Into the reaction flask, 1,5-cyclooctadiene iridium chloride dimer (0.1 mol% to 2 mol% of substrate in Formula 1) andChiral phosphine ligands (0.22 mol% to 4.4 mol% of substrate in Formula 1)And solvent (1 mL),Stir at room temperature for 10 minutes;The catalyst was then transferred to substrate 1a (62.2 mg, 0.3 mmol)Additive N-bromosuccinimide (10 mol% -150 mol% of substrate in Formula 1)And base (0-75 mol% of substrate in Formula 1)Amp bottle, and add solvent 2mL,The reaction flask was then transferred to a high pressure reactor,Hydrogen (500 psi to 1000 psi)At 0 -80 for 24-36 hours;Hydrogen was released and the pure product was obtained by direct column chromatography after removing the solvent. |
82 % ee | With N-Bromosuccinimide; chloro(1,5-cyclooctadiene)rhodium(I) dimer; hydrogen; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,2-dichloro-ethane at 0℃; for 36h; Glovebox; Overall yield = 92 %; enantioselective reaction; | 2 Condition A: In the glove box,The reaction flask was charged with 1,5-cyclooctadiene iridium chloride dimer(2 mol% of substrate in Formula 1) and(R) -BINAP (4.4 mol% of substrate in Formula 1)And solvent 1,2-dichloroethane (1 mL),Stir at room temperature for 10 minutes;The catalyst was then transferred to substrate 1 (0.3 mmol)Additive N-bromosuccinimide (10 mol% of substrate in Formula 1) Ampere bottle,And add 2mL solvent,The reaction flask was then transferred to a high pressure reactor,Hydrogen (1000 psi)At 0 ° C for 36 hours;Hydrogen was released, and the solvent was removed and directly purified by column chromatography to obtain the pure product S configuration product (S) -2. |
86 % ee | With Cp*Ir(biot-p-L)Cl; streptavidin S112A-N118P-K121A mutant; sodium formate In aq. buffer at 37℃; for 48h; enantioselective reaction; | |
78 % ee | With Cp*Ir(biot-p-L)Cl; streptavidin S112R-N118P-K121A-S122M-L124Y mutant; sodium formate In aq. buffer at 37℃; for 48h; enantioselective reaction; | |
64 % ee | With sodium formate; sodium hydroxide In aq. buffer at 37℃; for 48h; | |
60 % ee | With recombinant FPD-chimera streptavidin Sav-FPD; [Cp*Ir(biot-p-L)Cl] In dimethyl sulfoxide at 25℃; for 16h; Enzymatic reaction; enantioselective reaction; | |
85 % ee | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C42H46FeP2; hydrogen; trifluoroacetic acid In tetrahydrofuran at 30℃; for 12h; Autoclave; Schlenk technique; enantioselective reaction; | |
54 % ee | With Cp*Ir(biot-p-L)Cl; MASMTGGQQMGRDQAGITGTWYNQLGSTFIVTAGADGALTGTYESAVGNAESRYVLTGRYDSAPATDGSGTALGWTVAWKNNYRNAHSATTWSGQYVGGAEARINTQWLLTAGTTEANAWASTLVGHDTFTKVKPSAASIDAAKKAGVNNGNPLDAVQQGSGGGNGGGNGGGNGGGNIDGRGGGNASMTGGQQMGRDQAGITGTWYNQLGSTFIVTAGADGALTGTYVTARGNAESRYVLTGRYDSAPATDGSGTALGWTVAWKNNYRNAHSATTWSGQYVGGAEARINTQWLLTAGTTEANAWASTLVGCDTFTKVKPSAASIDAAKKAGVNNGNPLDAVQQ In dimethyl sulfoxide at 25℃; for 24h; Sealed tube; | |
17 % ee | With Cp*Ir(biot-p-L)Cl; MASMTGGQQMGRDQAGITGTWYNQLGSTFIVTAGADGALTGTYESAVGNAESRYVLTGRYDSAPATDGSGTALGWTVAWKNNYRNAHSATTWSGQYVGGAEARINTQWLLTAGTTEANAWASTLVGHDTFTKVKPSAASIDAAKKAGVNNGNPLDAVQQGSGGGNGGGNGGGNGGGNIDGRGGGNASMTGGQQMGRDQAGITGTWYNQLGSTFIVTAGADGALTGTYVTARGNAESRYVLTGRYDSAPATDGSGTALGWTVAWKNNYRNAHSATTWSGQYVGGAEARINTQWLLTAGTTEANAWKSTLVGCDTFTKVKPSAASIDAAKKAGVNNGNPLDAVQQ In dimethyl sulfoxide at 25℃; for 24h; Sealed tube; | |
26 % ee | With 1-dodecyl-3-methylimidazolium bis(2,4,4-trimethylpentyl)phosphinate; C31H33ClN2O8RuS3(2-)*2Na(1+); sodium formate In n-heptane; water at 60℃; Inert atmosphere; Overall yield = 10 percentChromat.; enantioselective reaction; | |
49 % ee | With formic acid; C33H37ClN2O4RuS; triethylamine In dichloromethane at 20℃; for 96h; Inert atmosphere; Schlenk technique; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.1% | With water; potassium hydroxide; In dimethyl sulfoxide; at 120℃; for 10h; | The obtained solid, 1.7 L of dimethyl sulfoxide and 4.56 g of potassium hydroxide were added to a 1 L reaction flask, and the mixture was heated to 120 C for 10 hours, and the reaction solution was added to ice water. After stirring for 0.5 h, suction filtration and drying to give 139.6 g of a pale yellow solid ( intermediate 3 racemate). The yield was 92.1%, and the specific rotation was -0.3. |
With potassium hydroxide; water; In dimethyl sulfoxide; at 160℃; for 15h; | (1 R)-1 -phenyl- 1,2,3,4-tetrahydro-isoquinoline (5 g) recovered from the filtrate of the resolution step, potassium hydroxide (1.3 g), water (2.5 ml), and dimethyl sulfoxide (50 ml) were taken into a clean and dry round bottom flask and stirred for about 15 minutes. The reaction mixture was heated to about 160 0C and maintained for about 15 hours. Water (50 I) was added to the above reaction mixture and stirred for about 45 minutes. The separated solid was then filtered and washed with water (15 ml). The wet solid was taken into a separate round bottom flask and n-hexane (50 ml) was added and stirred for about 1 hour. The separated solid was filtered and washed with n-hexane (25 ml). The wet solid was dried at about 50 0C to afford 3.2 g of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: P2O5; POCl3 / xylene / 2.5 h / Heating 2: NaBH4 / ethanol / 60 h / 20 °C | ||
Multi-step reaction with 3 steps 1.1: PPA / water / 4.25 h / 14.9 - 165 °C 1.2: 0.17 h / 28 - 42 °C / pH 2.1 - 7.12 2.1: methanol; sodium tetrahydroborate / water / 5.42 h / 20 - 34 °C 3.1: potassium hydroxide / water; dimethyl sulfoxide / 11.83 h / Heating / reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: K2CO3 / CH2Cl2 / 20 °C 2: NaH / toluene / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: K2CO3 / CH2Cl2 / 20 °C 2: NaH / toluene / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: 97 percent / CH2Cl2 / 20 °C 2.1: NaBH4; BF3*OEt2 / tetrahydrofuran / 2 h / 20 °C 2.2: 90 percent / NaOH / H2O / 1 h / Heating 3.1: 85 percent / 120 °C 4.1: t-BuLi / diethyl ether; pentane / 0.17 h / -90 °C 4.2: 78 percent / Et2AlCl / hexane / -90 - 20 °C 5.1: PCC; NaOAc; 3A molecular sieves / CH2Cl2 / 48 h / 20 °C 5.2: 82 percent / KOH / tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: potassium tert-butoxide / tetrahydrofuran / 0.5 h / 0 °C 1.2: tetrahydrofuran / 12 h / 20 °C 1.3: 95 percent / formic acid / CH2Cl2 / 72 h / 20 °C 2.1: 97 percent / CH2Cl2 / 20 °C 3.1: NaBH4; BF3*OEt2 / tetrahydrofuran / 2 h / 20 °C 3.2: 90 percent / NaOH / H2O / 1 h / Heating 4.1: 85 percent / 120 °C 5.1: t-BuLi / diethyl ether; pentane / 0.17 h / -90 °C 5.2: 78 percent / Et2AlCl / hexane / -90 - 20 °C 6.1: PCC; NaOAc; 3A molecular sieves / CH2Cl2 / 48 h / 20 °C 6.2: 82 percent / KOH / tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: NaBH4; BF3*OEt2 / tetrahydrofuran / 2 h / 20 °C 1.2: 90 percent / NaOH / H2O / 1 h / Heating 2.1: 85 percent / 120 °C 3.1: t-BuLi / diethyl ether; pentane / 0.17 h / -90 °C 3.2: 78 percent / Et2AlCl / hexane / -90 - 20 °C 4.1: PCC; NaOAc; 3A molecular sieves / CH2Cl2 / 48 h / 20 °C 4.2: 82 percent / KOH / tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 85 percent / 120 °C 2.1: t-BuLi / diethyl ether; pentane / 0.17 h / -90 °C 2.2: 78 percent / Et2AlCl / hexane / -90 - 20 °C 3.1: PCC; NaOAc; 3A molecular sieves / CH2Cl2 / 48 h / 20 °C 3.2: 82 percent / KOH / tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: t-BuLi / diethyl ether; pentane / 0.17 h / -90 °C 1.2: 78 percent / Et2AlCl / hexane / -90 - 20 °C 2.1: PCC; NaOAc; 3A molecular sieves / CH2Cl2 / 48 h / 20 °C 2.2: 82 percent / KOH / tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 1.) n-butyllithium / 1.) hexane, THF, -100 deg C, 15 min, 2.) THF, -85 to -100 deg C, 6 h 2: 48 percent / p-TsOH, conc. HCl / methanol; H2O / 96 h / Heating 3: 90 percent / LiAlH4 / tetrahydrofuran / 16 h / Heating 4: 68 percent / Na, liquid ammonia / tetrahydrofuran / 0.75 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 1.) n-butyllithium / 1.) hexane, THF, -100 deg C, 15 min, 2.) THF, -85 to -100 deg C, 6 h 2: 48 percent / p-TsOH, conc. HCl / methanol; H2O / 96 h / Heating 3: 90 percent / LiAlH4 / tetrahydrofuran / 16 h / Heating 4: 68 percent / Na, liquid ammonia / tetrahydrofuran / 0.75 h / -78 °C | ||
Multi-step reaction with 6 steps 1: 1.) n-butyllithium / 1.) hexane, THF, -100 deg, 2 h, 2.) THF, 0 deg C, 2 h 2: 53 percent / ammonium cerium(IV) nitrate / methanol; H2O / 3 h / Ambient temperature 3: 81 percent / Et3N / tetrahydrofuran / 8 h / Ambient temperature 4: 48 percent / p-TsOH, conc. HCl / methanol; H2O / 96 h / Heating 5: 90 percent / LiAlH4 / tetrahydrofuran / 16 h / Heating 6: 68 percent / Na, liquid ammonia / tetrahydrofuran / 0.75 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 1.) n-butyllithium / 1.) hexane, THF, -100 deg, 2 h, 2.) THF, 0 deg C, 2 h 2: 53 percent / ammonium cerium(IV) nitrate / methanol; H2O / 3 h / Ambient temperature 3: 81 percent / Et3N / tetrahydrofuran / 8 h / Ambient temperature 4: 48 percent / p-TsOH, conc. HCl / methanol; H2O / 96 h / Heating 5: 90 percent / LiAlH4 / tetrahydrofuran / 16 h / Heating 6: 68 percent / Na, liquid ammonia / tetrahydrofuran / 0.75 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 53 percent / ammonium cerium(IV) nitrate / methanol; H2O / 3 h / Ambient temperature 2: 81 percent / Et3N / tetrahydrofuran / 8 h / Ambient temperature 3: 48 percent / p-TsOH, conc. HCl / methanol; H2O / 96 h / Heating 4: 90 percent / LiAlH4 / tetrahydrofuran / 16 h / Heating 5: 68 percent / Na, liquid ammonia / tetrahydrofuran / 0.75 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 48 percent / p-TsOH, conc. HCl / methanol; H2O / 96 h / Heating 2: 90 percent / LiAlH4 / tetrahydrofuran / 16 h / Heating 3: 68 percent / Na, liquid ammonia / tetrahydrofuran / 0.75 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 90 percent / LiAlH4 / tetrahydrofuran / 16 h / Heating 2: 68 percent / Na, liquid ammonia / tetrahydrofuran / 0.75 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 81 percent / Et3N / tetrahydrofuran / 8 h / Ambient temperature 2: 48 percent / p-TsOH, conc. HCl / methanol; H2O / 96 h / Heating 3: 90 percent / LiAlH4 / tetrahydrofuran / 16 h / Heating 4: 68 percent / Na, liquid ammonia / tetrahydrofuran / 0.75 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 13 percent / H2 / Pd/C / ethanol / 48 h 2: 42 percent / LiAlH4 / diethyl ether / 48 h / 0 °C | ||
Multi-step reaction with 2 steps 1: H2 / Pd/C / ethanol / 48 h / Ambient temperature 2: LiAlH4 / diethyl ether / 48 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
R.7 Starting compound: (1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline REFERENCE EXAMPLE 7 (1R)-Ethyl 1-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate Starting compound: (1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline Elemental analysis (for C18 H19 NO2); Specific optical rotation [α]D25: 199.2 (C=1.03,CHCl3) Mass analysis (m/z, FAB): 282 (M+ +1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; In water; dimethyl sulfoxide; for 11.8333h;Heating / reflux;Purification / work up; | (1 R)-1 -phenyl-1 ,2,3,4-tetrahydroisoquinoline (25 g) recovered from the filtrate of the resolution step, potassium hydroxide (15.5 g), water (12.5 mL), and dimethyl sulfoxide (50 mL) were placed into a clean and dry round bottom flask and stirred for 5 minutes. The reaction mixture was heated to reflux and maintained for 11 hours, 45 minutes. The reaction mass was cooled to 28C and chilled water (375 ml) was added to the reaction mixture and stirred for 35 minutes. The separated solid was then filtered, washed with water (25 mL) and dried at about 55C to afford 13 g of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In dichloromethane at -10 - 20℃; | 7 To a dry 100 mL three neck flask, enantiomerically enriched (lR)-l-phenyl- 1,2,3,4-tetrahydroisoquinoline (5 g), dichloromethane (25 mL) and triethylamine (2.5 g) were charged at room temperature. The reaction mixture was cooled to -10 to -5 °C. Then acetyl chloride (2.0 g) was added drop by drop over a period of 15 min. at -5 to 5 °C. The reaction mixture was warmed to room temperature and was stirred for 3-4 h at room temperature. Then again triethylamine (1.75 g) was added and the reaction mixture was cooled to -10 to -5 °C. Then acetyl chloride (1.4 g) was added drop by drop over a period of 10 min. at -5 to 5 °C. The reaction mixture was warmed to room temperature and stirred for 6-7 h at room temperature. To the reaction mixture water was added and was transferred into a separating funnel. The organic layer was separated and washed with water and brine solution. The organic layer was dried over anhydrous sodium sulfate. The solvent was then distilled out completely under a reduced pressure on Buchi rotavapour to obtain enantiomerically enriched N-acetyl- (lR)-phenyl-l,2,3,4-tetrahydroisoquinoline (Wt.-5.8 g; % Purity by HPLC-96.1 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In dichloromethane at 0 - 25℃; | 9 To a dry lOOmL three neck flask, enantiomerically enriched (lR)-phenyl- 1,2,3,4-tetrahydroisoquinoline (2.0g) was dissolved in 20mL dichloromethane, 1.45g anhydrous potassium carbonate were charged at 20-25 0 C. The reaction mixture was cooled to 0 to 5 °C, 1.93g 4-nitrophenyl chloroformate was charged portion wise at 0 to 5 °C, was stirred at 20-25 °C for 2 hr and subsequently cold water was added in to reaction mixture. The reaction mixture was transferred into a separating funnel and organic layer was separated, washed with water and brine solution, dried over anhydrous sodium sulfate. The solvent was then distilled out completely under a reduced pressure on Buchi rotavapour to obtain N-protected l-phenyl-1,2,3,4- tetrahydroisoquinoline (Wt.-3.8 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: D-tartaric acid / water / 1.5 h / 65 - 95 °C / Resolution of racemate 4.1: sodium methylate / toluene / 5 °C / Inert atmosphere; Reflux 4.2: 60 °C / Reflux | ||
Multi-step reaction with 3 steps 1.1: potassium carbonate / dichloromethane / 0 - 25 °C 2.1: sodium hydroxide / ethanol / 75 - 80 °C 2.2: Cooling 3.1: sodium methylate / toluene / 5 °C / Inert atmosphere; Reflux 3.2: 60 °C / Reflux | ||
Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 32 h / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: D-tartaric acid / water / 1.5 h / 65 - 95 °C / Resolution of racemate 4.1: sodium methylate / toluene / 5 °C / Inert atmosphere; Reflux 4.2: 60 °C / Reflux |
Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: D-tartaric acid / water / Resolution of racemate 3.2: 20 °C 4.1: sodium methylate / toluene / 5 °C / Inert atmosphere; Reflux 4.2: 60 °C / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: D-tartaric acid / water / 1.5 h / 65 - 95 °C / Resolution of racemate | ||
Multi-step reaction with 2 steps 1.1: potassium carbonate / dichloromethane / 0 - 25 °C 2.1: sodium hydroxide / ethanol / 75 - 80 °C 2.2: Cooling | ||
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 32 h / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: D-tartaric acid / water / 1.5 h / 65 - 95 °C / Resolution of racemate |
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: D-tartaric acid / water / Resolution of racemate 3.2: 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: D-tartaric acid / water / 1.5 h / 65 - 95 °C / Resolution of racemate 4.1: acetone / 5 °C / Reflux | ||
Multi-step reaction with 3 steps 1.1: potassium carbonate / dichloromethane / 0 - 25 °C 2.1: sodium hydroxide / ethanol / 75 - 80 °C 2.2: Cooling 3.1: acetone / 5 °C / Reflux | ||
Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 32 h / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: D-tartaric acid / water / 1.5 h / 65 - 95 °C / Resolution of racemate 4.1: acetone / 5 °C / Reflux |
Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: D-tartaric acid / water / Resolution of racemate 3.2: 20 °C 4.1: acetone / 5 °C / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: water | ||
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / -10 - 20 °C 2.1: hydrogenchloride; water; phosphoric acid / 32 h / 95 - 100 °C 2.2: 20 °C / pH 9 - 10 3.1: water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In dichloromethane at -10 - 20℃; | 2 To a dry 250 mL three neck flask, enantiomerically enriched (lR)-l-phenyl- 1,2,3,4-tetrahydroisoquinoline (10 g), dichloromethane (100 mL) and triethylamine (5.22 g) were charged at room temperature. The reaction mixture was cooled to -10 to -5 °C. Then chloroacetyl chloride (6.0 g) was added drop by drop over a period of 1 h at -5 to 5 °C. The reaction mixture was warmed to room temperature and stirred for 4-5 h at room temperature. To the reaction mixture, water and dichloromethane were added. It was transferred into a separating funnel. The organic layer was separated and washed with a brine solution. The organic layer was dried over anhydrous sodium sulfate. The solvent was then distilled out completely under a reduced pressure on Buchi rota vapor to obtain enantiomerically enriched N-chloroacetyl-(lR)-phenyl- 1,2,3,4-tetrahydroisoquinoline as a liquid (Wt.-13.5 g; % Purity by HPLC-97.4 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-nitrophenyl-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate With sodium hydroxide In ethanol at 75 - 80℃; Stage #2: With water Cooling; | 9 A solution of sodium hydroxide (2.0g) in absolute alcohol was added & refluxed at 75- 80 °C for 4 to 5 hrs. Subsequently, solvent was distilled out completely under a reduced pressure on Buchi rotavapor and cold water was added. The solid was filtered, wash with water & dried. Wt. of l-phenyl-l,2,3,4-tetrahydroisoquinoline was 1.0 g. (% Purity by HPLC-96.23 %, % Chiral purity of R-isomer 60.26 % & S-isomer 39.74 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Resolution of (R:S)-1 -phenyl- 1,2,3,4-tetrahydroisoquinoline (100 g) was carried out using (D)-(-)-tartaric acid in water as per the literature method known in the art (Ref 1.- J. Chem. Soc. Perkin. Trans I, (4), 869-73 (1988), Ref. 2.- Monatshefte Fur. Chemie, vol. 53-54:956-962(1929)) and diastereomeric (D)-(-)-tartaric acid salt of (1S)- 1 -phenyl- 1,2,3,4-tetrahydroisoquinoline was filtered out as a solid. The filtrate containing enantiomerically enriched (D)-(-)-tartaric acid salt of (lR)-l-phenyl-l,2,3,4- tetrahydroisoquinoline was collected and a clear aqueous solution 40 % aq. sodium hydroxide (NaOH, 85 mL) was added at room temperature when solid was precipitated. The precipitated solid was filtered and washed with water and dried. The weight of enantiomerically enriched (lR)-l-phenyl-l,2,3,4-tetrahydroisoquinoline was 61.0 g. (% Purity by HPLC-97.0 %; % Chiral purity of R-isomer -79.0 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: hydrogenchloride; water; phosphoric acid / 95 - 100 °C 1.2: 20 °C / pH 9 - 10 2.1: D-tartaric acid / water / Resolution of racemate 2.2: 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 2-chloropyridine; trifluoromethylsulfonic anhydride / dichloromethane / -78 - 20 °C / Inert atmosphere 2: 1,1'-bis-(diphenylphosphino)ferrocene; bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; iodine / dichloromethane / 24 h / 20 °C / 38002.6 Torr / Inert atmosphere; Autoclave | ||
Multi-step reaction with 2 steps 1.1: phosphorus pentoxide; trichlorophosphate / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / 140 °C 1.2: 1 h 2.1: bis(1,5-cyclooctadiene)diiridium(I) dichloride; phosphoric acid; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; potassium iodide / tetrahydrofuran / 16 h / 50 °C / 22502.3 Torr | ||
Multi-step reaction with 3 steps 1.1: phosphorus pentoxide; trichlorophosphate / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / 140 °C 1.2: 1 h 2.1: palladium on activated charcoal; hydrogen / 30 °C / 3750.38 Torr 3.1: trifluoroacetic acid / methanol; ethanol; hexane / 25 °C / Resolution of racemate |
Multi-step reaction with 2 steps 1.1: trifluoromethylsulfonic anhydride / dichloromethane / -78 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: formic acid; [N-[(1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2,3,4,5,6-η)-1,3,5-trimethylbenzene]ruthenium; triethylamine / isopropyl alcohol / 16 h / 30 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: phosphoric acid / 4 h / 180 °C 2: D-glucose; NADP; imine reductase from Stackebrandtia nassauensis; BmGDH / dimethyl sulfoxide; aq. phosphate buffer / 12 h / 30 °C / pH 7 / Enzymatic reaction | ||
Multi-step reaction with 2 steps 1: 2-chloropyridine; trifluoromethylsulfonic anhydride / dichloromethane / -78 - 20 °C / Schlenk technique 2: C42H46FeP2; trifluoroacetic acid; hydrogen; bis(1,5-cyclooctadiene)diiridium(I) dichloride / tetrahydrofuran / 12 h / 30 °C / 38002.6 Torr / Autoclave; Schlenk technique | ||
Multi-step reaction with 2 steps 1: polyphosphoric acid / 4 h / 190 °C / Inert atmosphere 2: triethylamine; formic acid; C33H37ClN2O4RuS / dichloromethane / 96 h / 20 °C / Inert atmosphere; Schlenk technique |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 0 - 20 °C 2: 2-chloropyridine; trifluoromethylsulfonic anhydride / dichloromethane / -78 - 20 °C / Inert atmosphere 3: 1,1'-bis-(diphenylphosphino)ferrocene; bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; iodine / dichloromethane / 24 h / 20 °C / 38002.6 Torr / Inert atmosphere; Autoclave | ||
Multi-step reaction with 3 steps 1.1: dichloromethane / 2 h / 0 - 5 °C 1.2: 6 h / 0 °C / Reflux 2.1: phosphorus pentoxide; trichlorophosphate / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / 140 °C 2.2: 1 h 3.1: bis(1,5-cyclooctadiene)diiridium(I) dichloride; phosphoric acid; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; potassium iodide / tetrahydrofuran / 16 h / 50 °C / 22502.3 Torr | ||
Multi-step reaction with 4 steps 1.1: dichloromethane / 2 h / 0 - 5 °C 1.2: 6 h / 0 °C / Reflux 2.1: phosphorus pentoxide; trichlorophosphate / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / 140 °C 2.2: 1 h 3.1: palladium on activated charcoal; hydrogen / 30 °C / 3750.38 Torr 4.1: trifluoroacetic acid / methanol; ethanol; hexane / 25 °C / Resolution of racemate |
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 0.25 h / 0 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: trifluoromethylsulfonic anhydride / dichloromethane / -78 °C / Inert atmosphere 2.2: Inert atmosphere 3.1: formic acid; [N-[(1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2,3,4,5,6-η)-1,3,5-trimethylbenzene]ruthenium; triethylamine / isopropyl alcohol / 16 h / 30 °C / Inert atmosphere | ||
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 12 h / 0 - 30 °C 2: phosphoric acid / 4 h / 180 °C 3: D-glucose; NADP; imine reductase from Stackebrandtia nassauensis; BmGDH / dimethyl sulfoxide; aq. phosphate buffer / 12 h / 30 °C / pH 7 / Enzymatic reaction | ||
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 12 h / 0 °C / Schlenk technique 2: 2-chloropyridine; trifluoromethylsulfonic anhydride / dichloromethane / -78 - 20 °C / Schlenk technique 3: C42H46FeP2; trifluoroacetic acid; hydrogen; bis(1,5-cyclooctadiene)diiridium(I) dichloride / tetrahydrofuran / 12 h / 30 °C / 38002.6 Torr / Autoclave; Schlenk technique | ||
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane 2: polyphosphoric acid / 4 h / 190 °C / Inert atmosphere 3: triethylamine; formic acid; C33H37ClN2O4RuS / dichloromethane / 96 h / 20 °C / Inert atmosphere; Schlenk technique |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 0 - 20 °C 2: 2-chloropyridine; trifluoromethylsulfonic anhydride / dichloromethane / -78 - 20 °C / Inert atmosphere 3: 1,1'-bis-(diphenylphosphino)ferrocene; bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; iodine / dichloromethane / 24 h / 20 °C / 38002.6 Torr / Inert atmosphere; Autoclave | ||
Multi-step reaction with 3 steps 1.1: dichloromethane / 2 h / 0 - 5 °C 1.2: 6 h / 0 °C / Reflux 2.1: phosphorus pentoxide; trichlorophosphate / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / 140 °C 2.2: 1 h 3.1: bis(1,5-cyclooctadiene)diiridium(I) dichloride; phosphoric acid; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; potassium iodide / tetrahydrofuran / 16 h / 50 °C / 22502.3 Torr | ||
Multi-step reaction with 4 steps 1.1: dichloromethane / 2 h / 0 - 5 °C 1.2: 6 h / 0 °C / Reflux 2.1: phosphorus pentoxide; trichlorophosphate / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / 140 °C 2.2: 1 h 3.1: palladium on activated charcoal; hydrogen / 30 °C / 3750.38 Torr 4.1: trifluoroacetic acid / methanol; ethanol; hexane / 25 °C / Resolution of racemate |
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 0.25 h / 0 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: trifluoromethylsulfonic anhydride / dichloromethane / -78 °C / Inert atmosphere 2.2: Inert atmosphere 3.1: formic acid; [N-[(1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2,3,4,5,6-η)-1,3,5-trimethylbenzene]ruthenium; triethylamine / isopropyl alcohol / 16 h / 30 °C / Inert atmosphere | ||
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 12 h / 0 - 30 °C 2: phosphoric acid / 4 h / 180 °C 3: D-glucose; NADP; imine reductase from Stackebrandtia nassauensis; BmGDH / dimethyl sulfoxide; aq. phosphate buffer / 12 h / 30 °C / pH 7 / Enzymatic reaction | ||
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 12 h / 0 °C / Schlenk technique 2: 2-chloropyridine; trifluoromethylsulfonic anhydride / dichloromethane / -78 - 20 °C / Schlenk technique 3: C42H46FeP2; trifluoroacetic acid; hydrogen; bis(1,5-cyclooctadiene)diiridium(I) dichloride / tetrahydrofuran / 12 h / 30 °C / 38002.6 Torr / Autoclave; Schlenk technique | ||
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane 2: polyphosphoric acid / 4 h / 190 °C / Inert atmosphere 3: triethylamine; formic acid; C33H37ClN2O4RuS / dichloromethane / 96 h / 20 °C / Inert atmosphere; Schlenk technique |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: (R)-quinuclidin-3-ol With bis-(p-nitrophenyl) carbonate In N,N-dimethyl-formamide at 25 - 30℃; Stage #2: (R)-(-)-1-phenyl-1,2,3,4-tetrahydroisoquinoline In N,N-dimethyl-formamide at 25 - 30℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 3-quinuclidinol With bis-(p-nitrophenyl) carbonate In N,N-dimethyl-formamide at 25 - 30℃; Stage #2: (R)-(-)-1-phenyl-1,2,3,4-tetrahydroisoquinoline In N,N-dimethyl-formamide at 25 - 30℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: 1-phenyl-3,4-dihydroisoquinoline With N-Bromosuccinimide; bis(1,5-cyclooctadiene)diiridium(I) dichloride; sodium carbonate; (+)-(R)-[2,3,2',3'-tetrahydro-5,5'-bi(1,4-benzodioxin)-6,6'-diyl]bis(diphenylphosphane) In 1,2-dichloro-ethane at 20℃; for 0.166667h; Stage #2: With hydrogen In 1,2-dichloro-ethane at 30℃; for 24h; enantioselective reaction; | |
94% | With N-Bromosuccinimide; bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; sodium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl In 1,2-dichloro-ethane at 30℃; for 24h; Glovebox; enantioselective reaction; | |
94% | With N-Bromosuccinimide; chloro(1,5-cyclooctadiene)rhodium(I) dimer; hydrogen; sodium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,2-dichloro-ethane at 30℃; for 24h; Glovebox; enantioselective reaction; | 2 Condition B: In the glove box,The reaction flask was charged with 1,5-cyclooctadiene iridium chloride dimer(1 mol% of substrate in Formula 1) and(R) -BINAP (2.2 mol% of substrate in Formula 1)And solvent 1,2-dichloroethane (1 mL),Stir at room temperature for 10 minutes;The catalyst was then transferred to substrate 1 (0.3 mmol)Additive N-bromosuccinimide (150 mol% of substrate in Formula 1)And base (75mol% of the amount of substrate in Formula 1) Ampere bottle,And add 3mL solvent,The reaction flask was then transferred to a high pressure reactor,Hydrogen (500 psi) was bubbledAt 30 for 24 hours;Hydrogen was released and the solvent was removed and purified by direct column chromatography to give pure R configuration (R) -2. |
Multi-step reaction with 2 steps 1: bis(1,5-cyclooctadiene)diiridium(I) dichloride; (R)-3,5-diMe-Synphos; hydrogen; N,N,N',N'-tetramethyl-1,8-diaminonaphthalene / 1,4-dioxane / 18 h / 20 °C / 22502.3 Torr / Inert atmosphere 2: samarium diiodide; water; triethylamine / tetrahydrofuran / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: bis(1,5-cyclooctadiene)diiridium(I) dichloride; (R)-3,5-diMe-Synphos; hydrogen; N,N,N',N'-tetramethyl-1,8-diaminonaphthalene / 1,4-dioxane / 18 h / 40 °C / 7500.75 Torr / Inert atmosphere 2: samarium diiodide; water; triethylamine / tetrahydrofuran / 20 °C / Inert atmosphere | ||
97 % ee | With hydrogen In tetrahydrofuran; toluene at 30℃; for 17h; Autoclave; enantioselective reaction; | |
> 99 % ee | With D-Glucose; NADPH at 30℃; for 24h; Enzymatic reaction; enantioselective reaction; | |
95 % ee | With Cp*Ir(biot-p-L)Cl; streptavidin S112A-N118P-K121A-S122M mutant In aq. buffer at 37℃; for 4h; Sealed tube; Enzymatic reaction; enantioselective reaction; | |
92 % ee | With Cp*Ir(biot-p-L)Cl; streptavidin S112A-N118P-K121A-S122M mutant; sodium formate In aq. buffer at 37℃; for 48h; enantioselective reaction; | |
Multi-step reaction with 2 steps 1: methanol; sodium tetrahydroborate / water / 5.42 h / 20 - 34 °C 2: potassium hydroxide / water; dimethyl sulfoxide / 11.83 h / Heating / reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; (S)-2,2',6,6'-tetramethoxy-4,4'-bis(diphenylphosphino)-3,3'-bipyridine; phosphoric acid In tetrahydrofuran at 65℃; for 20h; optical yield given as %ee; | ||
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; phosphoric acid; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; potassium iodide In tetrahydrofuran at 50℃; for 16h; optical yield given as %ee; | ||
Multi-step reaction with 2 steps 1: palladium on activated charcoal; hydrogen / 30 °C / 3750.38 Torr 2: trifluoroacetic acid / methanol; ethanol; hexane / 25 °C / Resolution of racemate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With hydrogenchloride; 5%-palladium/activated carbon; hydrogen In ethanol; ethyl acetate at 20℃; for 24h; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; (R<SUB>ax</SUB>,S,S)-C<SUB>3</SUB>-TunePhos / dichloromethane; tetrahydrofuran / 20 h / 30 °C / 31029.7 Torr / Autoclave; Glovebox 2: hydrogen; hydrogenchloride; 5%-palladium/activated carbon / ethanol; ethyl acetate / 24 h / 20 °C / 760.05 Torr / Schlenk technique | ||
Multi-step reaction with 2 steps 1: bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; (+)-(R)-[2,3,2',3'-tetrahydro-5,5'-bi(1,4-benzodioxin)-6,6'-diyl]bis(diphenylphosphane) / dichloromethane; tetrahydrofuran / 20 h / 30 °C / 31029.7 Torr / Autoclave; Glovebox 2: hydrogen; hydrogenchloride; 5%-palladium/activated carbon / ethanol; ethyl acetate / 24 h / 20 °C / 760.05 Torr / Schlenk technique |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; trichloroisocyanuric acid; hydrogen; (R)-segphos; In tetrahydrofuran; at 80℃; under 62059.4 Torr; for 48h;Glovebox; Autoclave;Catalytic behavior; | General procedure: In a glove box filled with nitrogen, a (1,5-cyclooctadiene)iridium chloride dimer (0.0025 mmol, 1.7 mg) was charged.Add 1 ml of tetrahydrofuran to the reaction flask with chiral ligand (R)-SegPhos (0.0055 mmol), and stir at room temperature for 10-30 minutes.The addition of trichloroisocyanuric acid (TCCA) (0.092 mmol) was then added for 10-30 minutes with the addition of isoquinoline (0.25 mmol) and 2 mL of tetrahydrofuran.The reaction flask was placed in a stainless steel autoclave, passed through 1200 psi of hydrogen, and reacted at 80 degrees for 20-48 hours.The hydrogen was slowly released, and the system was stirred with a saturated aqueous solution of Na 2 CO 3 for 10 minutes, and then extracted three times with dichloromethane.The organic phases were combined and dried, and the solvent was removed by a rotary evaporator and directly subjected to column chromatography (the ratio of the eluent petroleum ether to ethyl acetate was 10:1 to 5:1).The pure product is isolated and the reaction is as follows: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trichloroisocyanuric acid In dichloromethane at 3 - 5℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With dimethyl sulfoxide at 100℃; for 24h; Schlenk technique; Green chemistry; chemoselective reaction; | General Procedure for Dehydrogenation of Tetrahydroisoquinolines General procedure: 1-substituted-1,2,3,4-tetrahydroisoquinolines 1 (0.3 mmol) were placed in a Schlenk tube and then DMF (1 mL) was added. The mixture was stirred at 100 °C for 24 h. Then the mixture was slowly cooled to room temperature, the solvent DMF was carefully removed under vaccum, the crude product was purified by flash chromatography on silica gel employing petroleum ether and ethyl acetate as eluent to give the corresponding product imines 2. |
Multi-step reaction with 2 steps 1: trichloroisocyanuric acid / dichloromethane / 1.5 h / 3 - 5 °C 2: potassium hydroxide / methanol / 1 h / 20 °C | ||
With hydrogenchloride; oxygen In aq. phosphate buffer at 37℃; |
With air In N,N-dimethyl-formamide at 100℃; for 24h; Schlenk technique; Green chemistry; | 3 Example 3: Chiral Tetrahydroisoquinoline Racemization Test A single enantiomer 1-phenyl-1,2,3,4-tetrahydroisoquinoline substrate (84 mg, 0.4 mmol, 96.9% ee) was added to the reaction flask, dissolved in DMF and heated to 100 ° C The reaction was carried out for 24 hours. The reaction was carried out by thin layer chromatography until the raw material completely disappeared. Then, the solvent was removed under reduced pressure and no other treatment was carried out to give 1-phenyl-3,4-dihydroisoquinoline, (30 mg, 0.8 mmol) of sodium borohydride was added at room temperature and the reaction was stirred at room temperature. The reaction was carried out by thin layer chromatography to complete disappearance of the starting material. A small amount of water was quenched by the addition of ethyl acetate The organic phase was washed three times with the organic phase and saturated brine, dried over anhydrous sodium sulfate, concentrated and chromatographed to give 71.1 mg, 84.6% yield, and 0.3% ee by HPLC. The method can realize the racemization of tetrahydroisoquinoline substrate and has certain application value in industrial reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: dimethyl sulfoxide / 24 h / 100 °C / Schlenk technique; Green chemistry 2: acetonitrile / 8 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: dimethyl sulfoxide / 24 h / 100 °C / Schlenk technique; Green chemistry 2: acetonitrile / 8 h / Reflux 3: tetrahydrofuran; diethyl ether / 0.5 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: dimethyl sulfoxide / 24 h / 100 °C / Schlenk technique; Green chemistry 2.1: acetonitrile / 8 h / Reflux 3.1: tetrahydrofuran; diethyl ether / 0.5 h / Reflux 4.1: 5%-palladium/activated carbon; hydrogen / acetic acid / 9 h / 20 °C / 760.05 Torr 4.2: 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: trifluoroacetic acid / dichloromethane / 3 h / Inert atmosphere 2: titanium(IV) isopropylate; toluene-4-sulfonic acid; iodine / toluene / Inert atmosphere; Glovebox 3: hydrogen / tetrahydrofuran; toluene / 17 h / 30 °C / 45603.1 Torr / Autoclave | ||
Multi-step reaction with 2 steps 1: hydrogenchloride / dichloromethane; diethyl ether / 6 h / 20 °C / Inert atmosphere 2: bis(1,5-cyclooctadiene)diiridium(I) dichloride; C45H36F6FeN2P2S; hydrogen; titanium(IV) isopropylate / dichloromethane / 24 h / 25 °C / 22801.5 Torr / Inert atmosphere; Glovebox; Autoclave |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: trifluoroacetic acid / dichloromethane / 3 h / Inert atmosphere 2: titanium(IV) isopropylate; toluene-4-sulfonic acid; iodine / toluene / Inert atmosphere; Glovebox 3: hydrogen / tetrahydrofuran; toluene / 17 h / 30 °C / 45603.1 Torr / Autoclave |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: tetrahydrofuran / 0.25 h / 0 - 20 °C 2: trifluoroacetic acid / dichloromethane / 3 h / Inert atmosphere 3: titanium(IV) isopropylate; toluene-4-sulfonic acid; iodine / toluene / Inert atmosphere; Glovebox 4: hydrogen / tetrahydrofuran; toluene / 17 h / 30 °C / 45603.1 Torr / Autoclave |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: tetrahydrofuran / 0.25 h / 0 - 20 °C 2: trifluoroacetic acid / dichloromethane / 3 h / Inert atmosphere 3: titanium(IV) isopropylate; toluene-4-sulfonic acid; iodine / toluene / Inert atmosphere; Glovebox 4: hydrogen / tetrahydrofuran; toluene / 17 h / 30 °C / 45603.1 Torr / Autoclave |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: tetrahydrofuran / 0.25 h / 0 - 20 °C 2: trifluoroacetic acid / dichloromethane / 3 h / Inert atmosphere 3: titanium(IV) isopropylate; toluene-4-sulfonic acid; iodine / toluene / Inert atmosphere; Glovebox 4: hydrogen / tetrahydrofuran; toluene / 17 h / 30 °C / 45603.1 Torr / Autoclave | ||
Multi-step reaction with 3 steps 1: tetrahydrofuran / 0 - 20 °C / Inert atmosphere 2: hydrogenchloride / dichloromethane; diethyl ether / 6 h / 20 °C / Inert atmosphere 3: bis(1,5-cyclooctadiene)diiridium(I) dichloride; C45H36F6FeN2P2S; hydrogen; titanium(IV) isopropylate / dichloromethane / 24 h / 25 °C / 22801.5 Torr / Inert atmosphere; Glovebox; Autoclave |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: tetrahydrofuran / 0.25 h / 0 - 20 °C 2: trifluoroacetic acid / dichloromethane / 3 h / Inert atmosphere 3: titanium(IV) isopropylate; toluene-4-sulfonic acid; iodine / toluene / Inert atmosphere; Glovebox 4: hydrogen / tetrahydrofuran; toluene / 17 h / 30 °C / 45603.1 Torr / Autoclave |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: sodium hydride / tetrahydrofuran / 1 h / 0 °C 1.2: 12 h / 20 °C 2.1: tetrahydrofuran / 0.25 h / 0 - 20 °C 3.1: trifluoroacetic acid / dichloromethane / 3 h / Inert atmosphere 4.1: titanium(IV) isopropylate; toluene-4-sulfonic acid; iodine / toluene / Inert atmosphere; Glovebox 5.1: hydrogen / tetrahydrofuran; toluene / 17 h / 30 °C / 45603.1 Torr / Autoclave | ||
Multi-step reaction with 4 steps 1: triethylamine; dmap / dichloromethane / 6 h / 0 - 20 °C / Inert atmosphere 2: tetrahydrofuran / 0 - 20 °C / Inert atmosphere 3: hydrogenchloride / dichloromethane; diethyl ether / 6 h / 20 °C / Inert atmosphere 4: bis(1,5-cyclooctadiene)diiridium(I) dichloride; C45H36F6FeN2P2S; hydrogen; titanium(IV) isopropylate / dichloromethane / 24 h / 25 °C / 22801.5 Torr / Inert atmosphere; Glovebox; Autoclave |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: sodium hydride / tetrahydrofuran / 1 h / 0 °C 1.2: 12 h / 20 °C 2.1: tetrahydrofuran / 0.25 h / 0 - 20 °C 3.1: trifluoroacetic acid / dichloromethane / 3 h / Inert atmosphere 4.1: titanium(IV) isopropylate; toluene-4-sulfonic acid; iodine / toluene / Inert atmosphere; Glovebox 5.1: hydrogen / tetrahydrofuran; toluene / 17 h / 30 °C / 45603.1 Torr / Autoclave |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: titanium(IV) isopropylate; toluene-4-sulfonic acid; iodine / toluene / Inert atmosphere; Glovebox 2: hydrogen / tetrahydrofuran; toluene / 17 h / 30 °C / 45603.1 Torr / Autoclave | ||
75 % ee | With titanium(IV) isopropylate; bis(1,5-cyclooctadiene)diiridium(I) dichloride; C45H36F6FeN2P2S; hydrogen In dichloromethane at 25℃; for 24h; Inert atmosphere; Glovebox; Autoclave; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: titanium(IV) isopropylate; toluene-4-sulfonic acid; iodine / toluene / Inert atmosphere; Glovebox 2: hydrogen / tetrahydrofuran; toluene / 17 h / 30 °C / 45603.1 Torr / Autoclave |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 0.100 g 2: 0.070 g | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 80℃; for 16h; | 80.1 (S)-N-(2,4-dimethoxybenzyl)-4-((R)-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-N-(1,2,4- thiadiazol-5-yl)chromane-7-sulfonamide and (R)-N-(2,4-dimethoxybenzyl)-4-((R)-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-N-(1,2,4-thiadiazol-5-yl)chromane-7-sulfonamide To a solution of (R)-7-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)chroman-4-yl methanesulfonate (prepared according to Example 41, step 6, 0.32 g, 0.60 mmol) in tetrahydrofuran (6.0 mL) was added (R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (0.25 g, 1.2 mmol) and N,N-diisopropylethylamine (0.31 mL, 1.8 mmol). The mixture was heated to 80 °C. After 16 h, the reaction was diluted with dichioromethane (10 mL) and water (10 mL). The organic layer was removed and the aqueous layer was extracted with dichloromethane (2 x 10 mL). The combined organic layers were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was purified by column chromatography, eluting with 30% ethyl acetate in hexanes to afford the title compounds. Diastereomer 1: (S)-N-(2,4-dimethoxybenzyl)-4-((R)-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-N-(1,2,4-thiadiazol-5-yl)chromane-7-sulfonamide (stereochemistry at chromane arbitrarily assigned) Colorless solid (0.100 g, 26% yield). MS (ES+) m/z 655.1 (M + 1). Diastereomer 2: (R)-N-(2,4-dimethoxybenzyl)-4-((R)-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-N-(1,2,4-thiadiazol-5-yl)chromane-7-sulfonamide (stereochemistry at chromane arbitrarily assigned) Yellow solid (0.070 g, 18% yield). MS (ES+) m/z 655.1 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: air / N,N-dimethyl-formamide / 24 h / 100 °C / Schlenk technique; Green chemistry 2: sodium tetrahydroborate; methanol / 20 °C / Schlenk technique; Green chemistry 3: air / N,N-dimethyl-formamide / 24 h / 100 °C / Schlenk technique; Green chemistry |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94 % ee | With N-iodo-succinimide; bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; (R)-segphos In 1,4-dioxane at 80℃; for 48h; Autoclave; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94 % ee | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; trichloroisocyanuric acid; hydrogen; (R)-segphos In tetrahydrofuran at 80℃; for 48h; Autoclave; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96 % ee | With N-Bromosuccinimide; bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; sodium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl In 1,2-dichloro-ethane at 30℃; for 24h; Glovebox; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.9% | With water; sodium hydroxide In ethyl acetate at 20℃; | 2 Example 2 Fragment A The fourth step of the salt-split step of the second step of the salt-dissolved filtrate was steamed, and 2 L of deionized water was added to the obtained solid. Add 1 equivalent of 5M NaOH aqueous solution with stirring (in terms of theoretically remaining (R)-intermediate 4 and (S)-intermediate 4 in the filtrate), Then 900 ml of ethyl acetate was added and stirred at room temperature until clear. The organic layer was separated, washed successively with 120 ml of water and 225 ml of saturated sodium chloride solution, dried over anhydrous sodium sulfate and filtered. After drying the residue, 160.3 g of a white solid (mainly a fragment A isomer and a small portion of the fraction A) was obtained in a yield of 95.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: lithium chloride; water / dimethyl sulfoxide / 3 h / 130 °C / Inert atmosphere 2.1: borane-THF / tetrahydrofuran / 3 h / 75 °C 2.2: 3 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82 % ee | Stage #1: (R)-1-phenyl-1,4-dihydroisoquinolin-3(2H)-one With borane-THF In tetrahydrofuran at 75℃; for 3h; Stage #2: With hydrogenchloride In methanol; water at 20℃; for 3h; Overall yield = 47%; Overall yield = 6 mg; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: sodium carbonate / water / 0.25 h / 29.8 °C 1.2: 4.33 h / 17.5 - 26.6 °C 2.1: PPA / water / 4.25 h / 14.9 - 165 °C 2.2: 0.17 h / 28 - 42 °C / pH 2.1 - 7.12 3.1: methanol; sodium tetrahydroborate / water / 5.42 h / 20 - 34 °C 4.1: potassium hydroxide / water; dimethyl sulfoxide / 11.83 h / Heating / reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: sodium carbonate / water / 0.25 h / 29.8 °C 1.2: 4.33 h / 17.5 - 26.6 °C 2.1: PPA / water / 4.25 h / 14.9 - 165 °C 2.2: 0.17 h / 28 - 42 °C / pH 2.1 - 7.12 3.1: methanol; sodium tetrahydroborate / water / 5.42 h / 20 - 34 °C 4.1: potassium hydroxide / water; dimethyl sulfoxide / 11.83 h / Heating / reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 74 % ee 2: 55 % ee | With bis(1,5-cyclooctadiene)nickel (0); 7,9-bis(4-methyl-2,6-bis((R)-1-phenylethyl)phenyl)-7H-acenaphtho[1,2-d]imidazol-9-ium chloride; potassium <i>tert</i>-butylate; lithium tert-butoxide In Cyclopentane at 30℃; for 24h; Inert atmosphere; enantioselective reaction; |
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