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| CAS No. : | 136030-00-7 |
| Formula : | C9H11NO |
| M.W : | 149.19 |
| SMILES Code : | O[C@@H]1[C@H](N)C2=C(C=CC=C2)C1 |
| English Name : | (1R,2S)-1-Amino-2,3-dihydro-1H-inden-2-ol |
| MDL No. : | MFCD00216656 |
| GHS Pictogram: | |
| Signal Word: | |
| Hazard Statements: | |
| Precautionary Statements: | |
| Class: | |
| UN#: | |
| Packing Group: |
* 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 |
|---|---|---|
| 65% | at 0 - 20℃; for 96 h; | A 3 L round bottom flask was charged with diethyl MALONIMIDATE dihydrochloride (25.8 g, 0.112 moles, 1.0 equiv. ) and DIMETHYLFORMAMIDE (DMF) (320 mL). The mixture was cooled in an ice bath. To this suspension was added (LR, 2S)- (+)-CIS-L-AMINO-2- indanol (40 G, 0.268 moles, 2.4 equivalents), in portions, over twenty minutes. The ice bath then was removed, and the reaction allowed to warm to room temperature, during which time the reaction product precipitated from the reaction. After four days stirring at room temperature, the reaction was filtered. The collected white solid was suspended in CH2Cl2 (450 ML). The mixture then was washed with water (260 ML) and brine (260 mL). The organic lay- er was dried over sodium sulfate (NA2SO4), filtered, and concentrated to an off-white solid. Drying overnight under vacuum provided 23.9 g (65percent yield) of the bis (oxazoline) (4). 1H NMR (300 MHZ/CDCL3) : 6 7. 45 (m, 2H, Ar-H); 7.27-7. 21 (m, 6H, AR-H) ; 5.56 (d, J=7.9 Hz, 2H, N-CH); 5.34 (M, 2H, O-CH) ; 3.39 (DD, J=7.0, 18. 0 Hz, 2H, Ar-CHH); 3 : 26 (S, 2H, -CH2-0); 3.16 (d, J=18.0 Hz, 2H, 14-CHH). The'NMR is consistent with the peak assignments made in WO 00/15599. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | With potassium hydroxide In ethanol for 16h; Heating; | |
| 79% | With potassium hydroxide In ethanol for 24h; Heating; | |
| > 99 %Spectr. | With ammonium bromide; ethylenediamine at 80℃; for 5h; Microwave irradiation; | 5.7 After termination of the reaction, the reaction mixture was analyzed directly by 1H NMR spectroscopy in which the yield was calculated on the integrated intensity ratio of the starting materials and the product in 1H NMR spectrum. Yield more than 99%. |
[ 136030-00-7 ]
[ 84946-20-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 95% | With triethylamine In dichloromethane at 0℃; for 1.5h; | |
| 95% | With triethylamine In dichloromethane at 0℃; for 1.5h; | |
| 91% | With triethylamine In dichloromethane at 0℃; for 1.5h; Inert atmosphere; |
| 1.15 g | With triethylamine In dichloromethane at -60 - 20℃; for 1h; | |
| With triethylamine In dichloromethane | N-(3'-methanethiosulfonatopropyl)-(3aR-cis)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]-oxazol-2-one((R)-1i) (1R,2S)-cis-1-amino-2-indanol (0.980 g, 6.569 mmol) was placed in a round-bottomed flask and a dry Ar atmosphere was established. Dry CH2Cl2 (50 mL) and Et3N (1.9 mL, 13.63 mmol) were added, and the resulting solution was cooled to -60° C. On addition of triphosgene (0.64 g, 2.157 mmol), the cooling bath was removed, and the reaction was allowed to warm to 20° C. over one hour. The reaction was then poured into CH2Cl2 (100 mL) and H2O (50 mL) and the aqueous phase was extracted with CH2Cl2 (3*100 mL). After drying with MgSO4, the organic layer was evaporated under reduced pressure to give (3aR-cis)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]-oxazol-2-one, (R)-24 (1.15 g, quantitative) as white crystals, which was of sufficient purity for the next step in the reaction sequence. An analytical sample was recrystallized from CH2Cl2/hexanes. mp 205.5-206.5° C.; [Ghosh et al. (1992) J. Chem. Soc. Chem. Commun. 1673-1674 for enantiomer mp 205° C.]; [α]25D=+107.7 (c 1.25, CHCl3); [Id. for enantiomer [α]25D=-79.4 (c 1.4, CHCl3)]. IR (KBr) 3255, 1752, 1707 cm-1; 1H NMR (acetone-d6) δ 7.24-7.43 (4H, m), 5.39 (1H, t, J=7.5 Hz), 5.21 (1H, d, J=7.0 Hz), 3.42 (1H, dd, J=17.7, 6.2 Hz), 3.20 (1H, d, 17.9 Hz), 2.90 (1H, br s); 13C NMR (acetone-d6) δ 159.1, 142.5, 141.0, 129.7, 128.3, 126.2, 125.8, 80.8, 61.7, 39.3; HRMS (FAB+) m/z: calcd for C10H9NO2+H, 176.0771; found, 176.0681. | |
| 92% | With triethylamine In dichloromethane at 0 - 25℃; Inert atmosphere; | |
| 95 % | With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 66% | Stage #1: carbon dioxide; (1R,2S)-1-Amino-2-indanol With N(Et)4(1+)*(2-pyrrolidone-anion) In acetonitrile at 20℃; for 1h; Stage #2: With p-toluenesulfonyl chloride In acetonitrile at 20℃; Further stages.; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79% | With hydrogenchloride In chloroform at 60℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 58% | With sodium acetate In acetonitrile at 20℃; Electrolysis; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: formaldehyd; 2-(1-adamantyl)-4-methylphenol With 2,6-dimethylpyridine; tin(IV) chloride Stage #2: (1R,2S)-1-Amino-2-indanol |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | With zinc trifluoromethanesulfonate In toluene for 48h; Heating; | |
| 47% | With zinc trifluoromethanesulfonate In toluene at 130℃; for 72h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 100% | With zinc trifluoromethanesulfonate In toluene for 48h; Heating; | |
| 71% | Stage #1: 2,2-dimethylmalononitrile With zinc trifluoromethanesulfonate In toluene for 0.0833333h; Inert atmosphere; Stage #2: (1R,2S)-1-Amino-2-indanol In toluene for 24h; Reflux; Inert atmosphere; | |
| 64 % | With zinc trifluoromethanesulfonate In toluene at 130℃; Schlenk technique; | General procedure E: Alternative synthesis of bis(oxazoline)-ligands General procedure: In an oven dried Schlenk tube dimethyl malononitrile (1.00 eq.) was dissolved in dry PhMe (0.8 M with respect to the nitrile) and Zn(OTf)3 (2.00 eq.) was added. The corresponding aminoalcohol (2.00 eq.) was added and the mixture was heated to 130 °C for 3 d. After cooling to rt, it was washed with sat. aq. NaHCO3-sol. (1 ×) and brine (1 ×). The org. phase was dried over MgSO4, filtered and concentrated in vacuo. The product was obtained via FC, recrystallisation or distillation with the conditions given in the corresponding entry. |
| 12 % | With zinc trifluoromethanesulfonate In tetrahydrofuran at 120℃; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | In tetrahydrofuran at 0 - 20℃; | |
| 88% | In dichloromethane at 20℃; | |
| In tetrahydrofuran at 0 - 20℃; |
| In dichloromethane at 20℃; | ||
| In tetrahydrofuran for 0.5h; Cooling with ice; | ||
| 85 % | In dichloromethane at 20℃; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | With formic acid In toluene Heating; | |
| 90% | In toluene Heating / reflux; | 1 Synthesis and Characterization of 1 A mixture of cis-(1R,2S)-1-aminoindan-2-ol (5.0 g, 33.6 mmol) and 1,2-cyclohexanedione (1.8 g, 16.3 mmol) was refluxed in toluene using a Dean-Stark trap in the presence of catalytic amounts of formic acid until no water was formed. After cooling to room temperature, the solvent was removed under reduced pressure. The crude residue was dissolved in small amounts of dichloromethane and purified by crystallization upon addition of acetonitrile. Three crystallizations gave 5.5 g (14.5 mmol, 90%) of the product as a white powder. 1H NMR (300 MHz, CDCl3) δ=0.87 (d, J=12.0 Hz, 2H), 1.26-1.46 (m, 6H), 2.83 (bs, 2H), 3.13 (d, J=2.9 Hz, 4H), 4.69-4.74 (m, 2H), 5.01 (d, J=5.3 Hz, 2H), 7.17-7.26 (m, 6H), 7.37-7.43 (m, 2H). 13C NMR (75 MHz, CDCl3) δ=23.9, 37.2, 39.6, 69.9, 81.9, 102.1, 125.9, 126.0, 127.7, 128.6, 141.8, 144.6. Anal. Calcd C24H26N2O2: C, 76.98; H, 7.00; N, 7.48. Found: C, 76.66; H, 6.86; N, 7.40.; For example, employing (1R,2S)-cis-1-amino-2-indanol in the acid-promoted reaction with 1,2-cyclohexanedione, bisoxazolidine 1 was obtained in 90% yield and 99% de (FIG. 1B). It was shown that compound 1 was produced with excellent diastereoselectivity and exclusive formation of the (S,S)-N,O-diketal by crystallographic analysis: careful evaporation of a solution of 1 in chloroform gave the single crystal suitable for crystallographic analysis (CDCC602445). (Crystal structure data: C24H26N2O2, monoclinic, space group P21, a=16.9199(16) , b=5.5487(5) , c=23.585(2) , α=90.00°, β=108.5190(10)°, γ=90.00°, V=2099.6(3) 3, Z=4, ρcalcd=1.367 g cm-3, T=173 K.) |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In tetrahydrofuran at 0 - 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 93% | In ethanol for 0.0833333h; microwave irradiation; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: 40 percent / CH2Cl2 / Heating 2.1: TMEDA; iPr2NH; nBuLi / tetrahydrofuran / 3 h / -20 °C 2.2: 100 percent / tetrahydrofuran / 24 h / 60 °C | ||
| Multi-step reaction with 2 steps 1: triethylamine / CH2Cl2 / 2 h / 0 °C 2: 100 g / Ti(OiPr)4 / 8 h / 145 °C | ||
| Multi-step reaction with 2 steps 1.1: dichloromethane / 24 h / 45 °C / Inert atmosphere 2.1: sodium hydride / tetrahydrofuran; mineral oil / 30 min / 0 °C / Inert atmosphere 2.2: 3 h / 50 °C / Inert atmosphere |
| Multi-step reaction with 2 steps 1.1: dichloromethane / 12 h / 40 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 °C 2.2: 12 h / 20 °C |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: 70 percent / CH2Cl2 / 48 h 2: 82 percent / LiHMDS / tetrahydrofuran / 3 h / -78 °C | ||
| Multi-step reaction with 2 steps 1.1: dichloromethane / 24 h / 45 °C / Inert atmosphere 2.1: methyllithium / tetrahydrofuran / 30 min / -55 °C / Inert atmosphere 2.2: 3 h / 50 °C / Inert atmosphere | ||
| Multi-step reaction with 2 steps 1.1: dichloromethane / 12 h / 40 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 °C 2.2: 12 h / 20 °C |

[ 136030-00-7 ]
[ 67714-53-8 ]
[ 224311-51-7 ]
[ 865-48-5 ]
[ 535934-27-1 ]| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 184 mg (65%) | With sodium hydrogencarbonate; In water; ethyl acetate; toluene; | Preparation 1 (1R,2S)-1-[(3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol A solution of 3-chloro-2,5-diethylpyrazine (171 mg, 1.0 mmol), (1R,2S)-(+)-cis-1-amino-2-indanol (298 mg, 2.0 mmol), tris(dibenzylideneacetone)dipalladium (0) (28 mg, 0.03 mmol), and 2-(di-tertbutylphosphino)biphenyl (18 mg, 0.06 mmol) in toluene (2.0 mL) was purged with nitrogen and treated with sodium tertbutoxide (135 mg, 1.4 mmol). The resulting brown suspension was heated to 100° C. for 2 hours. At this time, the reaction was quenched with a saturated water solution of NaHCO3 and extracted twice with ethyl acetate (20 mL). The combined organics were washed with brine (15 mL), dried over MgSO4, filtered, and concentrated to give a black solid. This material was purified by biotage MPLC (40 g column, 25percent ethyl acetate/heptane) to afford 184 mg (65percent) of the title compound as a light purple solid. IR (diffuse reflectance) 3435, 3241, 2962, 2935, 2912, 2873, 1581, 1547, 1500, 1453, 1184, 1163, 1047, 744, 733 cm-1; OAMS supporting ions at: ESI+384.0; MS (CI) m/z 284 (MH+); HRMS (FAB) calcd for C17H21N3O +H1 284.1763, found 284.1754. [alpha]25D=12 (c 0.55, methylene chloride); Anal. Calcd for C17H21N3O: C, 72.06; H, 7.47; N, 14.83. Found: C, 72.15; H, 7.53; N, 14.42. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86% | Stage #1: potassium trifluoro-(5-formylfuran-2-yl)boranuide; (1R,2S)-1-Amino-2-indanol In methanol at 20℃; for 2h; Stage #2: With borane pyridine complex In methanol for 16h; Stage #3: With potassium hydrogen bifluoride In methanol; acetone for 2h; Further stages.; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86% | With sodium hydride In tetrahydrofuran | |
| 60% | Stage #1: (1R,2S)-1-Amino-2-indanol With sodium hydride In tetrahydrofuran; mineral oil at 0 - 70℃; for 0.916667h; Inert atmosphere; Schlenk technique; Stage #2: chloroacetic acid ethyl ester In tetrahydrofuran; mineral oil at 0℃; for 2.33333h; Reflux; Inert atmosphere; Schlenk technique; | |
| 57% | With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 4h; |
| Stage #1: (1R,2S)-1-Amino-2-indanol With sodium hydride In tetrahydrofuran at -10 - 70℃; Inert atmosphere; Stage #2: chloroacetic acid ethyl ester In tetrahydrofuran at -10 - 70℃; for 1.58333h; Inert atmosphere; | ||
| With sodium hydride In tetrahydrofuran Schlenk technique; | ||
| 95 % | With sodium hydride In tetrahydrofuran at 0℃; | 1.1 Add 9.0g (1R,2S)-1-amino-2-indanol to 400mL tetrahydrofuran, cool the solution to 0 degrees, then add 2.52g 60% sodium hydride, stir for half an hour, then add 7.1mL chloroacetic acid Ethyl esters continue to react.After stirring and reacting for 4 hours, samples were taken to monitor the reaction progress (TLC detection).After the reaction is complete, the reaction system is quenched with saturated aqueous sodium bicarbonate solution, extracted with ethyl acetate, the combined organic phases are dried with anhydrous sodium sulfate and filtered, and the organic phase is concentrated and recrystallized to obtain the product.10.7 g of white solid product was obtained with a yield of 95%. |
| Stage #1: (1R,2S)-1-Amino-2-indanol With sodium hydride In tetrahydrofuran at 0℃; Stage #2: chloroacetic acid ethyl ester In tetrahydrofuran | 1.1 (1) Synthesis of intermediate (4aR,9aS)-4,4a,9,9a-tetrahydroindeno[2,1-b][1,4]oxazin-3(2hydrogen)-one, reaction formula and the synthesis steps are as follows: Add 9.0g (1R,2S)-1-amino-2-indanol to 300mL tetrahydrofuran solution, cool to 0 degrees, then add 2.52g 60% sodium hydride, stir for half an hour, then add 7.1mL ethyl chloroacetate . After stirring for 4 hours, samples were taken to monitor the reaction progress (TLC detection). After the reaction was complete, the reaction system was quenched with saturated sodium bicarbonate, then extracted with ethyl acetate solution, and then the combined organic phase was dried with anhydrous sodium sulfate, and the product was obtained by recrystallization. Compound B was obtained as a solid product. | |
| 95 % | Stage #1: (1R,2S)-1-Amino-2-indanol With sodium hydride In tetrahydrofuran at 0℃; Stage #2: chloroacetic acid ethyl ester In tetrahydrofuran at 0℃; | 1.1 Add 9.0g (1R,2S)-1-amino-2-indanol to 400mL tetrahydrofuran, cool the solution to 0 degrees, then add 2.52g 60% sodium hydride, stir for half an hour, then add 7.1mL chloroacetic acid Ethyl esters continue to react.After stirring and reacting for 4 hours, samples were taken to monitor the reaction progress (TLC detection).After the reaction is complete, the reaction system is quenched with saturated aqueous sodium bicarbonate solution, extracted with ethyl acetate, the combined organic phases are dried with anhydrous sodium sulfate and filtered, and the organic phase is concentrated and recrystallized to obtain the product.10.7 g of white solid product was obtained with a yield of 95%. |
| 95 % | Stage #1: (1R,2S)-1-Amino-2-indanol With sodium hydride In tetrahydrofuran at 0℃; Stage #2: chloroacetic acid ethyl ester In tetrahydrofuran at 0℃; | 1.1 (1) Synthesis of intermediate ((4aR,9aS)-4,4a,9,9a-tetrahydroindeno[2,1-b][1,4]oxazin-3-one, reaction formula and synthesis steps are as follows: Add 9.0g (1R,2S)-1-amino-2-indanol to 300mL tetrahydrofuran solution, cool to 0 degrees, then add 2.52g 60% sodium hydride, stir for half an hour, then add 7.1mL ethyl chloroacetate . After stirring for 4 hours, samples were taken to monitor the reaction progress (TLC detection). After the reaction was complete, the reaction system was quenched with saturated sodium bicarbonate, then extracted with ethyl acetate solution, and then the combined organic phase was dried with anhydrous sodium sulfate, and the product was obtained by recrystallization. 10.7 g of solid product was obtained with a yield of 95% |
| 95 % | Stage #1: (1R,2S)-1-Amino-2-indanol With sodium hydride In tetrahydrofuran at 0℃; Stage #2: chloroacetic acid ethyl ester In tetrahydrofuran | 1.1 Add 9.0g (1R,2S)-1-amino-2-indenol to 400mL tetrahydrofuran, cool the solution to 0 degrees, then add 2.52g 60% sodium hydride, stir and react for half an hour,Add another 7.1 mL of ethyl chloroacetate to continue the reaction. After the stirring reaction for 4 hours, samples were taken to monitor the reaction progress (TLC detection). After the reaction is complete, the reaction system is quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, the combined organic phases are dried over anhydrous sodium sulfate and filtered, the organic phase is concentrated and recrystallized to obtain the product. 10.7 g of white solid product was obtained with a yield of 95% |
| Stage #1: (1R,2S)-1-Amino-2-indanol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; Stage #2: chloroacetic acid ethyl ester In tetrahydrofuran; mineral oil | 1.1 Add 9.0g (1R,2S)-1-amino-2-indenol to 300mL tetrahydrofuran solution, cool to 0 degrees, then add 2.52g 60% sodium hydride, stir for half an hour,Add another 7.1 mL of ethyl chloroacetate.Stir for 4 hours and take samples to monitor the reaction progress (TLC detection).After the reaction is complete, the reaction system is quenched with saturated sodium bicarbonate, and then extracted with ethyl acetate solution.The combined organic phases were then dried over anhydrous sodium sulfate and the product was obtained by recrystallization.Compound B was obtained as a solid product. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: (1R,2S)-1-Amino-2-indanol; 2-(1-hydroxy-4-carbonylcyclohexyl) ethyl acetate With titanium(IV) isopropylate Stage #2: With sodium tetrahydroborate In tetrahydrofuran at -20℃; optical yield given as %de; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 41% | Stage #1: 2-amino-1-(morpholin-4-yl)ethanone hydrochloride; <i>N</i>,<i>N</i>-dimethyl-formamide dimethyl acetal With pyrrolidine at 85℃; for 4h; Stage #2: (1R,2S)-1-Amino-2-indanol With acetic acid; N-methylaniline at 100℃; for 2h; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 46% | In dichloromethane for 18h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | With N-Bromosuccinimide; sulfuric acid at 0℃; | 26 Example 26: Kinetic Resolution of Racemic N-Heterocycles with a Recyclable , Polymer-Supported Reagent Example 26: Kinetic Resolution of Racemic N- Heterocycles with a Recyclable , Polymer- Supported Reagent This refers to the synthesis of a robust and recyclable polystyrene supported reagent and its use for the facile resolution of chiral amines. The resolutions are conducted simply by mixing the racemic amine and this reagent (~0.6 equiv) followed by aqueous extraction or column chromatography to separate the acylated product from the enantioenriched recovered amine. The reagent can be recycled dozens of times without loss of efficiency or selectivity. This approach is useful for obtaining enantiopure amines from their racemates, as well as preparing enantioenriched amides with groups that can be cleaved under mild conditions.Preparation of solid-supported amine resolving agent 9. Reagents and conditions: a) TFA:H2S0„ (3:1) 0 °C, then NBS (1.01 equiv), 80%; b) N, O-bis ( trimethylsilyl ) acetamide (1.1 equiv), CH3CN, 23 °C to 75 °C , then Mo05*PyHMPA (MoOPH) (1.2 equiv), CH2C12, 23 °C, 73%; c) benzylacrylate (1.50 equiv), Pd(OAc)2 (0.10 equiv), P(o-tolyl)3 (0.21 equiv) , Et3N (5.00 equiv) , CH3CN, 23 °C to 75 °C, 65%; d) Ac20 (1.10 equiv), EtOAc, 23 °C to 45 °C, then Pd/C (10 wt%), H2; then 1 M LiOH, 73%; e) 7(0.50 equiv), HATU (0.95 equiv), DMAP (1.00 equiv), Hiinig' s base (3.00 equiv), DMF; f) 3-phenylpropanoic anhydride, DMF, 45 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 76% | Stage #1: 4-(dimethylamino)picolinic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: (1R,2S)-1-Amino-2-indanol With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 18h; Inert atmosphere; | 4-(Dimethylamino)-N-((1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)picolinamide Anhydrous DMF (25 mL) was charged to a dried reactor charged with 4-(dimethylamino)picolinic acid (1.80 g, 12.1 mmol) and O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (4.26 g, 13 mol) under nitrogen at normal room temperature. Agitation was started and isopropyl ethylamine (2.31 mL, 13 mmol) was charged to the slurry. After agitating the slurry for 30 minutes, a homogeneous solution was obtained. (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol (2.05 g) was charged to the reactor as a solid followed by diisopropyl ethylamine (2.31 mL, 13 mmol). The reaction was agitated at normal room temperature under argon for 18 hours. 40 mL of water was charged to the reactor dropwise over 1 hour. The resulting slurry was agitated at normal room temperature for 1 hour. The solids were collected by filtration and washed with water followed by heptane. The solids were dried in a vacuum oven with a nitrogen stream at 70° C. for 2 days to provide the intended product 4-(dimethylamino)-N-((1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)picolinamide as an off white solid (2.74 g, 76% yield). 1H NMR (400 MHz, DMSO-D6) δ 8.77 (d, J=8.58 Hz, 1H), 8.15 (d, J=5.8 9 Hz, 1H), 7.37 (d, J=2.8 Hz, 1H), 7.29-7.13 (m, 4H), 6.76 (dd, J=5.9, 2.8 Hz, 1H), 5.45 (d, J=4.7 Hz, 1H), 5.34 (dd, J=8.7, 5.1 Hz, 1H), 4.51 (dd, J=4.71, 4.71, 4.71 Hz, 1H), 3.14 (dd, J=16.2, 4.8 Hz, 1H), 3.05 (s, 6H), 2.86 (d, J=16.2 Hz, 1H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 94% | Stage #1: (1R,2S)-1-Amino-2-indanol With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃; for 0.25h; Stage #2: Diethyl carbonate In tetrahydrofuran; hexane at 50 - 60℃; for 2h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 26.5 % ee | In water; isopropyl alcohol at 60℃; Overall yield = 50.9 %; Overall yield = 5.05 g; enantioselective reaction; | 1 (Example 1) Crude (S) -3-cyclohexane-1-carboxylic acid / (1R, 2S) -1-amino-3-cyclohexane-1-carboxylic acid (4.55 g), (1R, 2S) -1-amino-2-indanol (4.30 g) was added to water containing 2-propanol (45 mL), heated to 60 ° C. To dissolve the precipitate. The reaction solution was cooled to 50 ° C. and stirred for 2 hours after crystallization. It was gradually cooled to room temperature at 5 ° C / h and stirred for 12 hours. The precipitate was collected by filtration, washed with 2-propanol (10 mL), and dried under reduced pressure at 40 ° C. to obtain the title compound (5.05 g, 50.9%, 26.5% ee) as a white solid |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1.34 g | With acetic acid In toluene at 80℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 56% | With zinc(II) chloride In chlorobenzene at 140℃; for 24h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 43% | With zinc(II) chloride In chlorobenzene at 140℃; for 24h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 68% | With zinc(II) chloride In chlorobenzene at 140℃; for 24h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 43% | With zinc(II) chloride In chlorobenzene at 140℃; for 24h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 24% | With zinc(II) chloride In chlorobenzene at 140℃; for 24h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 53% | With 3,7-di([1,1′-biphenyl]-4-yl)-10-(naphthalen-1-yl)-10H-phenoxazine; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 24h; Inert atmosphere; Irradiation; Sealed tube; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: dichloromethane / 24 h / 45 °C / Inert atmosphere 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 °C / Inert atmosphere 2.2: 50 °C / Inert atmosphere | ||
| Multi-step reaction with 2 steps 1.1: dichloromethane / 24 h / 45 °C / Inert atmosphere 2.1: sodium hydride / tetrahydrofuran; mineral oil / 30 min / 0 °C / Inert atmosphere 2.2: 3 h / 50 °C / Inert atmosphere |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: dichloromethane / 24 h / 45 °C / Inert atmosphere 2.1: sodium hydride; sodium iodide / tetrahydrofuran; mineral oil / 0.67 h / 0 °C / Inert atmosphere 2.2: 20 h / 0 - 20 °C / Inert atmosphere |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: dichloromethane / 24 h / 45 °C / Inert atmosphere 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 20 °C 2.2: 4 h / Reflux |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80 % | With zinc trifluoromethanesulfonate In toluene Inert atmosphere; Reflux; Schlenk technique; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: (1R,2S)-1-Amino-2-indanol; 6-phenylpyridine-2-carbaldehyde In <i>tert</i>-butyl alcohol at 25℃; for 2h; Stage #2: With potassium carbonate In <i>tert</i>-butyl alcohol for 16h; Heating; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: dichloromethane / 12 h / 40 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 °C 2.2: 12 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: dichloromethane / 12 h / 40 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 °C 2.2: 12 h / 20 °C |
Tags: (1R,2S)-1-Amino-2-indanol | Benzene Compounds | Aryls | Chiral Building Blocks | Amines | Alcohols | Other Chiral Nitrogen Ligands | Asymmetric Synthesis | Organic Building Blocks | Chiral Nitrogen Ligands | 136030-00-7
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