| 90.5% |
With sodium tetrahydroborate; In methanol; at 20℃; |
To a 3 L four-necked flask, a solution of 178 g of the intermediate 2 in methanol (2 L) was added, and 64.3 g of sodium borohydride was slowly added. The reaction mixture is stirred at room temperature for about 3 to 4 hours, and the reaction solution is slowly poured into 4 L of ice water under stirring, suction-filtered, washed with water, and dried to obtain 161 g (90.5% of the intermediate 1) of the intermediate 3 solid |
| 89% |
With sodium tetrahydroborate; In methanol; at 20℃; |
compound VII 21.5g (theoretical containing 20.7g) is added to the 100 ml methanol, adding sodium borohydride at room temperature 3.8g, stirring the reaction, the reaction with 0.1mol/L dilute hydrochloric acid quenching, wash-out solid, filtering, compound VIII is obtained after drying by blowing. 18 . 6g, yield 89.0%. |
| 88% |
With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 3h; |
1-Phenyl-3,4-dihydroisoquinoline in methanol (4, 1.0 equiv) was taken in round bottom flask and then cooled to 0 C. Sodium borohydride (1.5 equiv.) was added in portions at 0 C and then slowly warmed to room temperature. After 3 h stirring, methanol was evaporated and the residue was taken in dichloromethane. Water was added in fractions and washed twice with dichloromethane. All the dichloromethane fractions were combined, dried over anhydrous Na2SO4, solvent was removed, purified by column chromatography using silica gel as stationary phase and mixture of ethyl acetate and hexanes as elutent to obtain pure racemic 1-phenyl-1,2,3,4-tetrahydroisoquinoline 5 in 88 % yield as white solid. rac-1-Phenyl-1,2,3,4-tetrahydroisoquinoline: 1H NMR (400 MHz, CD3OD) delta: 7.30-7.18 (m, 5H), 7.12-7.07 (m, 2H), 6.99-6.95 (m, 1H), 6.65 (d, J = 8.0 Hz, 1H), 5.02 (s, 1H), 3.08-2.92 (m, 3H), 2.75-2.84 (m, 1H). 13C NMR (100 MHz, CD3OD) delta: 142.4, 136.0, 133.4, 127.3, 127.1, 126.5, 126.2, 125.6, 124.6, 123.83, 59.9, 39.6, 27.0, LCMS (m/z): 210.16, m.f.: C15H15N. Elemental analysis (%): Calculated: C-86.08, H-7.22, N-6.69, Obtained: C-86.10, H-7.21, N-6.68. |
| 85% |
With sodium tetrahydroborate; In methanol; at 20℃; |
Using the above general procedure, (R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline 1a (84 mg, 0.4 mmol, 97% ee) was placed in a Schlenk tube and then DMF (2 mL) was added. The mixture was stirred at 100 C for 24 h. Then the mixture was slowly cooled to room temperature, and the solvent DMF was carefully removed under vaccum, the crude product without further purification. To a solution of the above mixture in methanol (3 mL) was added sodium borohydride (30 mg, 0.8 mmol). The resulting mixture was stirred at room temperature till imine was consumed determined by TLC. The mixture was extracted with dichloromethane twice and the combined organic extracts dried over sodium sulfate. The resulting mixture were concentrated in vaccum and purification was performed by a silica gel column eluted with petroleum ether/ethyl acetate to give the desired racemic product 1-phenyl-1,2,3,4-tetrahydroisoquinoline 1a (71 mg, 85% yield, 0.3% ee). Enantiomeric excess was determined by HPLC (OD-H column, hexane/ iPrOH 90/10, 1.0 mL/min, 230 nm, 30 C): t1= 6.3 min, t2= 9.5 min. |
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A solution of the compound obtained from step b above (4.2 g, 20.28 mmol) in ethanol (50 ml) was cooled in an ice bath followed by the addition of sodium borohydride (0.848 g, 22.31 mmol) in small lots and stirred the reaction mixture at room temperature for overnight. The reaction mixture was concentrated under reduced pressure and the residue thus obtained was taken in water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography using 45% ethyl acetate in hexane solvent mixture to furnish the title compound. Yield: 3.35g |
| 71.1mg |
With methanol; sodium tetrahydroborate; at 20℃;Schlenk technique; Green chemistry; |
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. |
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With sodium tetrahydroborate; In methanol; |
Xylene (80 ml), P2O5 (132.2 mmol) and POCl3 (66.10 mmol) were added to the solid and refluxed for 6 hours. After cooling to room temperature, water was added, the aqueous layer was basified with NaOH solution, extracted with dichloromethane, and the solvent was evaporated to obtain a residue. Sodium borohydride (33.31 mmol) was added portionwise to the methanol solution of the residue (22.21 mmol) at room temperature for 20-30 min. The reaction mixture was then stirred for 3-4 hours. After the reaction is complete (TLC EA: hexane = 3: 7), the solvent is distilled off and 10 ml of water + conc. HCl 5 ml was added to the reaction mixture. The reaction mixture was then extracted with methylene chloride. The aqueous layer was basified with 1N KOH and extracted with ethyl acetate. The solvent was evaporated to give a dark yellow residue which was used without purification in the next step |
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With bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen bromide; hydrogen; In tetrahydrofuran; water; at 20℃; under 38002.6 Torr; for 12h;Schlenk technique; |
Under the protection of nitrogen, [Ir(COD)Cl]2(1.6 mg, 0.0024 mmol) and the above bisphosphine ligand (4.2 mg, 0.0055 mmol) and 1 mL of tetrahydrofuran were placed in a Schlenk reaction tube, stirred for 30 min, and the catalyst solution was transferred to a hydrogenation tube, followed by 104 mg. Imine substrate and 7 muL aqueous hydrobromic acid solution (40%), then add 1 mL of tetrahydrofuran, three times with hydrogen, at room temperature and 50 atm H2The reaction was carried out for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the residue was dissolved in 10 mL of dichloromethane, washed with saturated sodium hydrogen carbonate solution, water and brine, dried over anhydrous sodium sulfate and evaporated to dryness. Column chromatography to obtain the new intermediate I,1H NMR detection reaction conversion > 99%, chiral HPLC detection of enantiomeric excess > 84%Ee. |
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