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CAS No. : | 2094-74-8 | MDL No. : | MFCD12031698 |
Formula : | C11H16O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | DZULQZKFBAHSRX-UHFFFAOYSA-N |
M.W : | 164.24 | Pubchem ID : | 11041050 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.91 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 48.59 |
TPSA : | 17.07 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.66 cm/s |
Log Po/w (iLOGP) : | 2.06 |
Log Po/w (XLOGP3) : | 2.31 |
Log Po/w (WLOGP) : | 2.4 |
Log Po/w (MLOGP) : | 2.59 |
Log Po/w (SILICOS-IT) : | 2.76 |
Consensus Log Po/w : | 2.43 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.25 |
Solubility : | 0.929 mg/ml ; 0.00565 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.31 |
Solubility : | 0.81 mg/ml ; 0.00493 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -1.89 |
Solubility : | 2.14 mg/ml ; 0.013 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 3.77 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338-P304+P340-P405 | UN#: | N/A |
Hazard Statements: | H302 | 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 |
---|---|---|
75% | With potassium carbonate In methanol at 20℃; for 4 h; | EXAMPLE 32 Preparation of 1-Ethynyladamantane To a stirred mixture of adamantane-1-carbaldehyde (2.0 g, 12.2 mmol) and K2CO3 (3.36 g, 24.4 mmol) in methanol (200 ml) is added dimethyl (1-diazo-2-oxopropyl)phosphonate (2.8 g, 14.6 mmol) dropwise. After stirring for 4 h at room temperature, the reaction mixture is diluted with ether (100 ml). The mixture is washed with NaHCO3 solution (5percent in water, 300 ml). The organic layer is separated, dried (MgSO4) and concentrated. The crude material is purified by chromatography (silica gel, 100percent hexane) to afford the title compound 1.5 g (75percent) as a white solid. mp: 80-82° C. MS (+) ES: 161 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | An oven-dried 3-neck flask equipped with 125-mL addition funnel was charged with anhydrous CH2Cl2 (150 mL) and anhydrous DMSO (10.3 mL, 0.145 mol, 2.5 equiv) under argon atmosphere and cooled to -78C. Slow dropwise addition of oxalyl chloride (6.7 mL, 0.0768 mol, 1.32 equiv) followed by stirring for 15 min provided an activated DMSO adduct. This was treated with a solution of Step 2 compound (9.67 g, 58.2 mmol, 1 equiv) in dry CH2Cl2 (75 mL) and the reaction allowed to stir for 1 h. The resulting white mixture was then treated dropwise with triethylamine (40.5 mL, 0.291 mol, 5 equiv). After 30 min, the cooling bath was removed, and the reaction quenched sequentially with cold 20% aq KH2PO4 (25 mL) and cold H2O (150 mL). After stirring at rt for 15 min the mixture was diluted with Et2O (400 mL) and the layers were separated. The organics were washed organic with cold 10% aq KH2PO4 (3x150 mL) and satd aq NaCl (100 mL). The organics were dried (Na2SO4), filtered and concentrated. The residue was purified by flash column chromatography on silica gel (5x10 cm) with CH2Cl2 to give the Step 3 compound as a white solid (9.40 g, 98%). | |
92% | General procedure: A solution of ion-supported methyl sulfide A-2 (C6) (2.0 mmol, 0.769 g) and alcohols (1.0 mmol) in CH2Cl2 (6 mL) was added to a CH2Cl2 (5 mL) solution of N-chlorosuccinimide (2.0 mmol, 0.267 g) at -40 C, and the obtained mixture was stirred for 0.5 h. Triethylamine (5.0 mmol, 0.506 g, 0.70 mL) was added to the mixture at -40 C, and the mixture was stirred for 14 h. The reaction mixture was quenched with H2O (20 mL), and extracted with diethyl ether (60 mL). The organic layer was washed by H2O (20 mL) and a satd aq NaHCO3 (30 mL×2). The organic layer was dried over Na2SO4 and concentrated in vacuo to provide aldehyde or ketone. The purity was estimated by 1H NMR measurements. | |
89% | With pyridinium chlorochromate; In dichloromethane; at 20℃; for 1.16667h; | Example 6 - Synthesis of secondary-amine-based adamantane-DFOB.The PCC-based oxidation of <strong>[770-71-8]1-adamantanemethanol</strong> will furnish 1- adamantanecarboxaldehyde in an 89% yield, as described in the literature [20]. The Schiff base condensation between 1 -adamantanecarboxaldehyde and DFOB will yield the imine-based adamantane-DFOB conjugate which will be reduced by sodium cyanoborohydride (NaCNBH3) to give the secondary amine-based adamantane-DFOB conjugate. Sodium cyanoborohydride does not reduce the hydroxamate groups of DFOB to amides [21]. |
86% | With pyridinium chlorochromate; In dichloromethane; at 20℃; for 1h; | To a suspension of pyridinium chloro chromate (23.17 g, 107.5 mmol) in DCM(150 mL) was added adamant- 1-ylmethanol (10.5 g, 63.2 mmol) in DCM (100 mL) under stirring. The resulting dark brown coloured reaction mixture was stirred at RT for 1 h. Reaction mixture was diluted with diisopropyl ether (750 mL) and filtered through celite, the filtrate was washed with aqueous IN NaOH (1 x 250 mL ) solution and water (2 x 150 mL). The organic layer was dried over anhydrous sodium sulphate, concentrated to afford the pure title compound (8.94 g, 86% yield). |
85% | With pyridinium chlorochromate; In Dichlorodifluoromethane; at 20℃; for 2h; | EXAMPLE 31 Preparation of Adamantane-1-carbaldehyde To a suspension of pyridinium chlorochromate (3.88 g, 18 mmol) in methylene chloride (100 ml) is added a solution of <strong>[770-71-8]1-adamantanemethanol</strong> (2.0 g, 12 mmol) in methylene chloride (30 ml) in one portion. After stirring for 2 h at room temperature, the reaction mixture is diluted with ether (50 ml). The mixture is filtered through a funnel packed with silica gel (20 g) and washed with ether. The filtrate is concentrated to afford the title compound 1.7 g (85%) as a white solid. mp: 132-135 C. MS (+) ES: 165 (M+H)+. |
83% | With pyridinium chlorochromate; In dichloromethane; at 0 - 20℃; for 1.66667h; | 1-adamantanecarboaldehyde (49)To a solution of <strong>[770-71-8]1-adamantanemethanol</strong> (1.66g, lOmmol) in CH2Cl2 was added PCC (4.3g, 20mmol) at 00C. The resulting mixture was stirred at the same temperature for lOmins before warming to ambient temperature. Stirring was continued for 1.5hrs until thedisappearance of starting material as checked by TLC. Water was added and extracted with CH2Cl2 for 3 times. The combined organic phase was dried over MgSO4, filtrated and concentrated in vacuo. The crude mixture was separated by flash chromatography (50%- 100% CH2C12/Hexane) to give 49 as white solid (1.36g, Yield: 83%). 1H-NMR (360 MHz, CDCl3) delta 9.32 (s, IH), 2.07 (br s, 3H), 1.77 (br s, 6H), 1.72 (br s, 6H); 13C-NMR (90 MHz, CDCl3) delta 206.07, 45.03, 37.25, 36.10, 27.61; ESI-MS: Calculated for C11H16O (M + H)+ 165.2, Found: 165.5. |
76% | With 2-azatricyclo[3.3.1.13,7]dec-2-yloxidanyl; [bis(acetoxy)iodo]benzene; In N,N-dimethyl-formamide; at 20℃; for 2h;Inert atmosphere; | General procedure: To a solution of 1-(p-bromophenyl)ethanol I-23 (201 mg, 1.0 mmol) in DMF (2.0 mL) was added HIO3 (194 mg, 1.1 mmol) and TEMPO (7.8 mg, 0.05 mmol). The mixture was stirred for 2 h at room temperature under an Ar atmosphere. After the reaction, the reaction mixture was poured into aq Na2S2O3, and extracted with a mixture of Et2O: hexane=1:1 (3*10 mL). Then, the organic layer was poured into satd NaCl (10 mL) and extracted with Et2O (10 mL). The organic layer was dried over Na2SO4. After being filtration and removal of the solvent under reduced pressure, the residue was purified by flash short column chromatography on silica gel (EtOAc-hexane, 1:4) to give p-bromoacetophenone II-23 in 99% yield. |
74% | With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium bromide; In dichloromethane; water; for 0.333333h;pH 8.6;Cooling with ice; | General procedure: (1-Adamantyl)methanol (3.0 g, 18 mmol), KBr (214 mg, 1.8 mmol) and TEMPO (28 mg, 0.18 mmol)2 were dissolved in DCM (50 mL). The solution was cooled in an icebath. A commercial 5 % bleach-solution (30 mL) was buffered to pH 8.6 using solid NaHCO3 and then added to the TEMPOsolution. After 20 min of rapid stirring, the layers were separated. The DCM layer was dried over Na2SO4, filtered and concentrated in vacuo. This affords the product as a white to light-orange solid (2.25 g, 74%) |
71.2% | General procedure: A solution of BTC (0.41 g, 1.39 mmol) in dry CH2Cl2 (5 mL) was cooled in an ice-salt bath under an atmosphere of N2. A solution of I (1.24 g, 4.17 mmol) in dry CH2Cl2 (5 mL) was added dropwise for 0.5 h, at -15 C. Stirring was continued for 0.5 h, and a solution of benzyl alcohol (0.3 g, 2.78 mmol) in dry CH2Cl2 (5 mL) was added dropwise for 0.5 h, at-15 C. After stirring for 0.5 h, Et3N (0.84 g, 8.34 mmol) was added slowly while the temperature should be controlled below -15 C. When the reaction was completed, 10% HCl solution in water was added dropwise until the pH of the reaction solution reached 2 under ice bath. The mixture was extracted with n-hexane or petroleum ether (10 mL x 2),decanted. The product was acquired after organic layer was concentrated and purified by flash chromatography (SiO2; n-hexane). (0.27 g, 92%). The water layer was used for the recovery of V and the excess I. | |
With Dess-Martin periodane; In dichloromethane; at 0 - 20℃; for 1h; | Synthesis of Compound 704Adamantyl-methanol 701 (5.0 g, 30 mmol) was dissolved in 40 mL of dry dichloromethane and to it was added portion- wise Dess-Martin Periodinate (13 g, 32 mmol) at 00C. The resulting mixture was allowed to stir at room temperature for 1 h. After completion of the reaction, the reaction mixture was poured into water, and the organic layer was separated, washed with sodium bisulfite and brine, and dried over sodium sulfate. Evaporation of the organic layer provided 4.3 g of the corresponding aldehyde 702. | |
6%Chromat. | Cu/HT; In toluene; at 110℃; for 24h;Inert atmosphere;Product distribution / selectivity; | Example 3-15 A mixture of 1 mmol of 1-hydroxymethyladamantane, 5 mL of toluene, and 0.1 g (Cu: 3.0 percent by mole) of the catalyst prepared from Example 3-0 and including Cu particles immobilized on a hydrotalcite surface was stirred at 110 C. in an argon atmosphere for 24 hours and thereby yielded a corresponding carbonyl compound (1-adamantanal) in a yield equivalent to a gas chromatographic (GC) yield of 6%. |
0.052 g | General Procedure: To a dry 25 ml 3-neck round bottom flask equipped with magnetic stirring bar, thermometer, Ar inlet, and dropping funnel was added dry dimethyl sulfoxide (4 mmol, 0.32g, 0.29 ml) diluted with dry DCM ((3 ml), and the solution was cooled bellow -60 C in dry ice-acetone bath. Then trifluoroacetic anhydride (3 mmol, 0.63 g, 0.42 ml), in 2 ml of dry DCM was added. After 10 min of efficient stirring 1-adamantane methanol (2 mmol, 0.33 g) in 2 ml of dry DCM was added dropwise. The rate of addition of alcohol was controlled to keep temperature bellow -60 C. Mixture was stirred for 20 min at -65 C, then ice bath was removed and mixture was allowed to warm up to room temperature. Next, triethylamine (0.8 ml) was added in portions during 10 minutes, and mixture was stirred for another 10 minutes. The reaction mixture was poured into separatory funnel and washed with diluted HCl, then with water, and combined aqueous fractions were extracted once with DCM. Organic fractions were combined, dried over sodium sulfate, and solvent was evaporated. Residue was dried in vacuum giving yellow solid (0.052 g). | |
Example- 7; Charge MDC (400 ml) into dry RBF. Cool the reaction mass to 0-5C. Slowly add oxalyl chloride (150 gm) into the reaction mass at 0C-5C under nitrogen atmosphere. Stir the reaction mixture at 0C-5C for 10 minutes. Cool the reaction mass to -60 to -70C. Add DMSO (135 ml) and MDC (100 ml) solution to reaction mass at -60 to-70C. Stir for 10 minutes at -65C. Add compound XIV (100 gm) and MDC (600 ml) solution to reaction mass at -60 to -70C. Maintain the reaction mass for 30 min at -60 to -70C. Add triethylamine (420 ml) slowly to the reaction mass at -60 to-70C. Maintain the reaction mass for 20-30 min at -60 to-70C. Check TLC. Slowly raise the reaction mass temperature to 25 to35C. Quench reaction mass into KH2SO4 solution at 25 to35C. Stir the reaction mass for 10 minutes. Settle the reaction mass and separate the organic layer. Wash the MDC layer with KH2SO4 solution. Dry the MDC layer with sodium sulfate. Distill out the MDC completely under vacuum below 50C. Residue weight: 80 gm. (Compound XV). | ||
41 g | The 50g, (0.3 moles) of compound-II was dissolved in 500mL of MDC and76g (0.9M) of sodium bi carbonate and7.2g (0.06M) of KBr were added at room temperature and reaction mass was cooled to 0-5C and stirred for 15 minutes. O. l g of TEMPO solution was added at 0-5C and then 225mL of sodium hypo chloride (1 1% chlorine content) solution was slowly added for 60-90 minutes at 0-5 C. Reaction mass was stirred for 2-3 hours at 0-5C till reaction was completed. After completion of the reaction, 10% (500 ml) sodium bi sulphate solution was added at 0-5C. Temperature was slowly, raised to room temperature and 350mL of DM water was added and reaction mass was stirred for 30 minutes and both the layers were separated. The aqueous layer was extracted with 300mL of MDC and total organic layer was combined and organic layer was washed with 25mL saturated sodium chloride solution. The organic layer was dried over sodium sulphate and the organic layer was distilled under vacuum at below 35C to obtain 41 gm of semisolid Step-A aldehyde compound having 99 % of purity by GC analysis. | |
To a -60 C cold solution of 0.86 mL of oxalyl chloride (12.99 mmol, 1.2 eq) in 20 mL of abs. dichloromethane were added 2 mL of abs. DMSO dropwise and the solution was diluted with 5 mL of dichloromethane. Afterstirring for 30 min at -60 C a solution of 1.80 g of hydroxymethyladamantane, S14, (10.83 mmol, 1.0 eq) in 20mL of abs. dichloromethane was added and the mixture was stirred for 1 hour at -60 C. The reactions mixturewas brought to room temperature after adding 7.5 mL of triethylamin (54.1 mmol, 5.0 eq). Next 20 mL of water were added and the biphasic mixture was stirred for additional 15 min. The layers were separated and the aqueous phase was extracted twice with dichloromethane (75 mL). The combined organic phases were washedwith water (3 x 150 mL), dried over Na2SO4, filtered and the solvent was removed under reduced pressure to give 1.40 g (79%) white solid. | ||
46%Spectr. | In ethyl acetate; at 45℃; for 10h;Inert atmosphere; Irradiation; | General procedure: To a three-necked, cylindrical Pyrex glass reaction vessel equipped with a rubber balloon, rubberseptum, and glass stopper, a N2 atmosphere was introduced by flowing via cannula for 5 min. Au(0.6 wt %)/TiO2 (117.3 mg, 0.17 mol % Au), 1a (271.5 mg, 1.99 mmol), and dehydrated ethylacetate (25 mL) were added successively to the vessel. After N2 gas was reintroduced more than 5min, the rubber balloon was connected to the vessel and the mixture was sonicated. The vessel wasimmersed in a oil bath (kept at 45 oC) and stirred for 10 h under irradiation (lambda = 300-470 nm). 1HNMR analysis of this crude mixture using mesitylene as an internal standard indicated 97%conversion of 1a and the formation of 2a in 86% yield, as determined based on the signals at delta 3.61ppm and 2.94 ppm (shifted from 2.89 ppm due to the presence of ethyl acetate), respectively. Theproduct was purified by silica gel column chromatography (n-hexane/ethyl acetate 3:1) to afford 2a(180 mg, 66% yield, with inclusion of small amounts of unidentified impurities). |
135.9 g | With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium bromide; In dichloromethane; water; at 5 - 30℃; for 12h; | To a 2000 ml four-necked reaction flask was added 0.83 mol of adamantane-1-carboxylic acid, followed by the addition of 600 ml of THF to stir. After the basic solid was dissolved, the ice bath was cooled to about 5 C; 0.75 mol (28.3 g) of NaBH4 was added in portions and the temperature was controlled to (about 30min drop finished); retreat ice bath, natural Heat to room temperature (25-30 C) and at room temperature. The reaction was stirred at this temperature for 2 hours. After the disappearance of adamantane-1-carboxylic acid, the reaction system was cooled to ); reaction 12 hours after standing, the water phase with 500mlDCM extraction, combined organic phase. Washed twice with 500 ml of semi-saturated sodium bicarbonate (500 ml * 2), dried over anhydrous sodium sulfate for 15 min and then filtered. The filtrate was concentrated under reduced pressure at 45 C to give a red semi-solid compound adamantane-1-carbaldehyde (Formula II) 135.9g. Yield 99.4%, GC purity 95.5% (containing 4.2% TEMPO by-product). |
90%Spectr. | With Iron(III) nitrate nonahydrate; 9-azabicyclo<3.3.1>nonane-N-oxyl; In acetonitrile; at 20℃; for 6h;Green chemistry; | Fe (NO3) 3.9H2O (40.4 mg, 10 mol%), ABNO (7 mg, 5 mol%),Adamantane methanol (166 mg, 1 mmol) was added to a 10 ml reaction tube,Then add 2ml of acetonitrile as solvent, open reaction at room temperature,The degree of reaction was then checked by GC-MS. After the reaction, add internal biphenyl,Quantitative analysis of the product adamantane formaldehyde yield with GC. Reaction 6h, adamantane formaldehyde yield was 90%, selectivity greater than 99%. |
With pyridinium chlorochromate; In dichloromethane; at 0 - 20℃; for 2h; | To a stirred solution of compound 10 (1 g, 1 eq) in DCM (10 mL) at 0 00 P00 (1.42 g, 1.1 eq) was added portion wise. The resulting reaction mass was stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC. After completion, the resulting mixture was filtered over a pad of celite. The filtrate was washed with water; the organic layer was separated; dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide the title compound 11. | |
With pyridinium chlorochroniate; In ethanol; dichloromethane; at 20 - 25℃; for 1.5h; | To a suspension of 3 g of pyridinium chlorochroniate in 20 mL of anhydrous dichioromethane at 20-2.VC, was added a solution of ig of adamantylmethanol In dry ethanol. The mixture was stirred at room temperature over 90 mm and then wasfiltered under neutral silica. The filtrate was collected and the solvent removed under vacuum. The crude aldehyde was obtained and used at step 2 without further purification |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With thexylchloroborane-Me2SO4 In dichloromethane for 0.25h; Ambient temperature; | |
64% | With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 2h; | Hydroxymethyladamantane (S14) modified [10] To a 0 °C cold solution of 1.35 g of lithium aluminum hydride (35.6 mmol, 1.28 eq) in 45 mL of abs.tetrahydrofuran was added a solution of 5.0 g of adamantylcarboxylic acid, S13, (27.7 mmol, 1.0 eq) in 45 mL ofabs. tetrahydrofuran dropwise. The solution was stirred for 2 hours at room temperature. Then 1.35 mL of water were added carefully followed by 2.7 mL of 10% sodium hydroxide and 3.05 mL of water. The suspension was stirred for 60 min and filtered through a pressed plug of Celite.[11] The solvent was removed under reduced pressure. The residue was taken up in 150 mL of diethyl ether, washed with saturated sodium bicarbonate solution, dried over Na2SO4, filtered and the solvent was removed in vacuum to give 2.92 g (64%) white solid. |
62% | Stage #1: 1-Adamantanecarboxylic acid With lithium aluminium tetrahydride Stage #2: |
60% | With pyridine; lithium tri(t-butoxy)aluminum hydride; N,N-dimethylchloromethyleniminium chloride 1) CH3CN - THF, -30 deg C, 1 h, 2) -78 deg C, 10 min; dimethylchloromethyleniminium chloride is prepared previously in situ from oxalylchloride and DMF.; | |
(i) SOCl2, (ii) diglyme, Li<AlH(OtBu)3>; Multistep reaction; | ||
8 % Spectr. | With hydrogen; 2,2-dimethylpropanoic anhydride In tetrahydrofuran at 80℃; for 24h; | |
Multi-step reaction with 3 steps 1: 100 percent / diethyl ether; hexane; methanol / 3 h / 20 °C 2: 96 percent / LiAlH4 / tetrahydrofuran / 1.5 h / 0 - 20 °C 3: 98 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / 1 h / -78 °C | ||
Multi-step reaction with 2 steps 1: LiAlH4 2: 1.) DMSO, trifluoroacetic anhydride, 2.) Et3N / 1.) CH2Cl2, -60 deg C, 5 min, 2.) CH2Cl2 | ||
Multi-step reaction with 2 steps 1: LiAlH4 2: Pb(OAc)4 / acetic acid | ||
Multi-step reaction with 3 steps 1: sulfuric acid / 3 h / 80 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 1.25 h / 0 - 20 °C 3: pyridinium chlorochromate / dichloromethane / 1 h / 20 °C | ||
Multi-step reaction with 2 steps 1: (μ3,η2,η3,η5-acenaphthylene)Ru3(CO)7 / TETRAHYDROPYRANE / 18 h / 50 °C 2: tetrabutyl ammonium fluoride; water | ||
Multi-step reaction with 3 steps 1.1: potassium carbonate / acetone / 3 h / 25 - 35 °C 2.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 0 - 35 °C / Inert atmosphere 2.2: 0 - 5 °C 3.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.5 h / -70 - -60 °C / Inert atmosphere 3.2: -70 - -60 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: tris(pentafluorophenyl)borate / benzene-d6 / 72 h / 23 °C / Glovebox; Schlenk technique 2: hydrogenchloride; water / tetrahydrofuran / 3 h / 20 °C / Glovebox; Schlenk technique | ||
Multi-step reaction with 3 steps 1: sulfuric acid / 10 h / Reflux 2: lithium aluminium tetrahydride / diethyl ether / 20 h / Reflux 3: pyridinium chlorochromate | ||
Multi-step reaction with 2 steps 1: dimethylsulfide borane complex / tetrahydrofuran / 3 h / 0 - 20 °C 2: pyridinium chlorochromate / 2 h | ||
Multi-step reaction with 3 steps 1.1: thionyl chloride / 3 h / 20 °C 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 3.1: potassium bromide; sodium hydrogencarbonate / dichloromethane / 0.25 h / 0 - 5 °C 3.2: 0 - 5 °C | ||
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere; Schlenk technique 2: N-(2,2,6,6-tetramethyl-1-oxopiperidin-1-ium-4-yl)acetamide tetrafluoroborate; sodium hypochlorite / dichloromethane; water / 20 °C | ||
Multi-step reaction with 3 steps 1.1: methanol; diethyl ether; hexane / 3 h / 20 °C 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 1.5 h / 20 °C / Inert atmosphere 3.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1 h / -78 °C / Inert atmosphere 3.2: 0.5 h / -78 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 15 h / 0 - 25 °C / Inert atmosphere 2: oxalyl dichloride / dichloromethane; dimethyl sulfoxide / 1.42 h / -78 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 2.5 h / 0 - 30 °C 2: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite; sodium bromide / dichloromethane; water / 12 h / 5 - 30 °C | ||
Multi-step reaction with 2 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere 2.1: dimethyl sulfoxide; oxalyl dichloride / 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran / 0.5 h / -78 °C / Inert atmosphere 2.2: 2 h / 0 °C | ||
Stage #1: 1-Adamantanecarboxylic acid With 2,6-dimethylpyridine; (1,2-dimethoxyethane)dichloronickel(II); 4,4'-di-tert-butyl-2,2'-bipyridine; zinc; dimethyl dicarbonate In ethyl acetate for 0.25h; Inert atmosphere; Green chemistry; Stage #2: With diphenylsilane In ethyl acetate at 60℃; for 16h; Inert atmosphere; Green chemistry; | ||
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: lithium aluminium tetrahydride / diethyl ether; tetrahydrofuran / 20 h / 0 - 20 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / -78 °C / Inert atmosphere 2.2: -78 - 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: 4-methyl-morpholine / toluene / 1 h / 20 °C / Inert atmosphere; Sealed tube 2: bis-triphenylphosphine-palladium(II) chloride; Dimethylphenylsilane / toluene / 6 h / 80 °C / Inert atmosphere; Sealed tube |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene at 100℃; for 3h; | |
86 %Chromat. | With 2,2'-azobis-(2,4-dimethylvaleronitrile); tri-n-butyl-tin hydride In decane; toluene at 80℃; for 0.2h; Continuous microflow reactor; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With zinc(II) iodide | |
75.3% | With zinc(II) iodide In dichloromethane at 0℃; for 1h; | |
With zinc(II) iodide at 20℃; for 150h; |
With zinc(II) iodide In chloroform for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 94% 2: 21% | In tetrachloromethane at 0℃; for 3h; | |
94% | With 2,6-di-tert-butyl-4-methylpyridine; 5A molecular sieve In tetrachloromethane at 0℃; for 3h; Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium cyanide; pyridinium chlorochromate In tetrahydrofuran at 45℃; | |
With poly[4-(diacetoxyiodo)styrene]; 2,2,6,6-tetramethyl-piperidine-N-oxyl In acetone at 20℃; for 24h; | ||
98 mg | With 9-oxyl-9-azabicyclo<3.3.1>nonan-3-one; oxygen; nitric acid; sodium nitrite In water; acetonitrile at 23℃; for 8h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 80.5 mg 2: 82% | In chlorobenzene at 120℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With lithium sodium In tetrahydrofuran at 20℃; for 0.0833333h; ultrasonic irradiation; | |
75% | With sodium; lithium In tetrahydrofuran at 20℃; for 0.0833333h; | |
36% | With lithium In diethyl ether for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With hydrogenchloride; | Step 2: 1-Adamantanecarbaldehyde Under the protection of nitrogen atmosphere, methyl 1-Adamantanecarboxylate (3 g, 15.5 mmol) was dissolved in PhMe (80 mL), then cooled down to -78 C. and DIBAL-H (1.5M of toluene solution, 10.3 mL) was added dropwise. 4N HCl was carefully added dropwise to carry out a quench reaction, then poured into ice-water and extracted with EA. The combined organic phase was washed with saturated brine, dried and concentrated. The crude product was separated by column chromatography to give the desired product (2.1 g, yield 82%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With aluminum tri-bromide; carbon tetrabromide; methyl-cyclopentane In various solvent(s) at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With aluminum tri-bromide; carbon tetrabromide; methyl-cyclopentane; carbon monoxide In various solvent(s) at -45℃; for 1h; Yield given. Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With hydrazine In ethanol at 0℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | Stage #1: 1-Adamantanecarbaldehyde With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 0.5h; Stage #2: With hydroxylamine-O-sulfonic acid In tetrahydrofuran; diethylene glycol dimethyl ether at -30 - 0℃; for 1h; Stage #3: With tert-butylhypochlorite In tetrahydrofuran; diethylene glycol dimethyl ether; <i>tert</i>-butyl alcohol at 0℃; for 1h; | |
42% | Stage #1: 1-Adamantanecarbaldehyde With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 0.5h; Stage #2: With hydroxylamine-O-sulfonic acid In tetrahydrofuran; diethylene glycol dimethyl ether at 0℃; for 0.5h; | |
Stage #1: 1-Adamantanecarbaldehyde With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: With hydroxylamine-O-sulfonic acid In tetrahydrofuran; diethylene glycol dimethyl ether at -35 - 0℃; for 1h; Inert atmosphere; Stage #3: With tert-butylhypochlorite In tetrahydrofuran; diethylene glycol dimethyl ether; <i>tert</i>-butyl alcohol at 0℃; for 0.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 1-adamantanecarbonitrile With hydrogenchloride; tin(ll) chloride In diethyl ether at 0 - 25℃; for 22h; Stage #2: With water In diethyl ether at 20 - 60℃; | |
77% | With sodium hydride; zinc(II) chloride In tetrahydrofuran; mineral oil at 40℃; for 1h; Inert atmosphere; Sealed tube; | Reduction of Nitriles 1 and 3 to Aldehydes 2 and 4; General Procedure General procedure: To a mixture of NaH (60% dispersion in mineral oil; 60.0 mg, 1.50 mmol) and ZnCl2 (102 mg, 0.750 mmol) in a 25-mL sealed tube was added a solution of nitrile 1 or 3 (0.500 mmol) in THF (2.5 mL). The mixture was sealed and stirred at 40 °C. The reaction was quenchedby following one of the two protocols. Workup protocol 1: Upon full consumption of the nitrile (TLC or GC monitoring), silica gel (2.0 g) was added to the mixture and it was diluted with hexane (10 mL) at 0 °C. The resulting mixture was stirred for 1 h at 24 °C. The mixture was then filtered through layers of cottonand sand and washed with EtOAc. The volatile materials were removedin vacuo from the resulting filtrate. The crude residue was purified by flash column chromatography to give the corresponding aldehyde 2 or 4. Workup protocol 2: Upon full consumption of amide (TLC or GC monitoring), the reaction was quenched with pH 10 ammonium buffer at 0°C and the organic materials were extracted with CH2Cl2 (3 × 20 mL). The combined organic extracts were dried (MgSO4). The volatile materials were removed in vacuo and the resulting crude residue was purified by flash column chromatography to give the corresponding aldehyde 2 or 4. |
Multi-step reaction with 2 steps 1: CH2Cl2 / 120 h / Heating 2: 1) Et3SiH, 2) H2O / 1) CH2Cl2, 1 h room temperature; 4 h reflux, 2) heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Stage #1: Diethyl allylphosphonate With methyllithium In tetrahydrofuran at -78℃; for 0.25h; Stage #2: 1-Adamantanecarbaldehyde With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran at 20℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With boron trifluoride diethyl etherate In chloroform at 0 - 20℃; for 5.16667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium hydrogensulfite In methanol; water for 16h; Heating; | |
65% | With sodium hydrogensulfite In methanol; water; ethyl acetate at 0 - 20℃; for 18.25h; Heating / reflux; | 1.4 Step 3 compound (9.40 g, 57 mmol, 1 equiv) was suspended in HZ0 (145 mL) and cooled to 0°C. The mixture was treated with NAHSO3 (5.95 g, 57 mmol, 1 equiv), KCN (4.0 g, 59 mmol, 1.04 equiv), and a solution of (R)- (- )-phenylglycinol (8.01 g, 57 mmol, 1 equiv) in MeOH (55 mL). The resulting mixture was stirred at rt for 2 h, then refluxed for 16 h. The mixture was cooled to rt, and 200 mL of EtOAc added. After mixing for 15 min the layers were separated. The aqueous fraction was extracted with EtOAc. The combined EtOAc extracts were washed with brine (50 mL), dried over anhydrous NA2SO4, filtered and the filtrate concentrated. The product was purified by flash column chromatography on silica gel (6. 4X20 cm) with 20% EtOAc/hexanes to give the desired (R, S) product as a white solid (11.6 g, 37.4 mmol, 65%): MS M/E 311 (M+H) +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: 1-Adamantanecarbaldehyde; ethanolamine In <i>tert</i>-butyl alcohol at 20℃; for 0.5h; Inert atmosphere; Stage #2: With 1,3-Diiodo-5,5-dimethyl-2,4-imidazolidinedione; potassium carbonate In <i>tert</i>-butyl alcohol at 50℃; for 24h; Inert atmosphere; | |
70% | With iodine; potassium carbonate In <i>tert</i>-butyl alcohol at 70℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With trifluoroacetic acid | |
51% | With trifluoroacetic acid at 20℃; for 1h; | 1 EXAMPLE 1 l-Di(pyrrole-2-yl)methyladamantane: Obtained by reacting adamantane-1-carbaldehyde (222 mg, 1.36 mmol) with pyrrole (3.65 g, 55 mmol, 3.8 niL) in the presence of TFA (10 μL, 0.14 mmol). After stirring over 1 h at rt the reaction was quenched and worked-up following the general procedure. After chromatography reaction furnished 207 mg (51 %) of the product in the form of colorless crystals which were further purified by recrystallisation from benzene/hexane mixture to remove the traces of unreacted pyrrole. Colorless crystals, mp 168-169 0C; 1H NMR (CDCl3) £/ppm (600 MHz) 1.56-1.69 (m, 12H), 1.97 (br.s, 3H), 3.57 (s, IH)5 6.08-6.23 (m, 4H)5 6.60-6.69 (m, 2H)5 7.97 (br.s, 2H); 13C NMR (CDCl3) J/ppm (150 MHz) 28.6 (d, 3C), 36.7 (t, 3C)5 36.9 (s, 1C), 40.4 (t, 3C)5 51.4 (d, 1C), 106.5 (d, 2C)5 108.2 (d, 2C)5 115.7 (d, 2C)5 130.1 (s, 2C); IR (KBr) Wan 1 3369 (s), 2927 (m), 2903 (m), 2864 (m); MS m/z (%) 279 (100, M-H+); HRMS, calculated for C19H23N2 279.1861; observed 279.1859. |
Stage #1: pyrrole; 1-Adamantanecarbaldehyde With trifluoroacetic acid at 20℃; for 1h; Inert atmosphere; Stage #2: With sodium hydroxide In water Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 65 percent / NaHSO3 / H2O; methanol / 16 h / Heating 2: 78 percent / aq. HCl; AcOH / 18 h / 80 °C 3: H2; AcOH / Pd(OH)2/C / methanol / 18 h / 2585.74 Torr 4: 4.07 g / K2CO3 / dimethylformamide / 19 h | ||
Multi-step reaction with 4 steps 1: sodium hydrogensulfite / 0 - 60 °C 2: hydrogenchloride; water / acetic acid / 80 °C 3: hydrogen; palladium 10% on activated carbon / acetic acid 4: triethylamine / methanol | ||
Multi-step reaction with 4 steps 1.1: sodium hydrogensulfite / methanol; water / 0 - 55 °C 2.1: hydrogenchloride; acetic acid; water / 20 - 95 °C 3.1: acetic acid; hydrogen; 10% palladium hydroxide on charcoal / methanol / 20 °C 4.1: sodium hydroxide / water / 0.25 h / 0 - 5 °C 4.2: 0 - 5 °C |
Multi-step reaction with 4 steps 1: sodium hydrogensulfite / methanol; water / 18 h / 0 - 20 °C / Reflux 2: hydrogenchloride; water / acetic acid / 18 h / 80 °C 3: hydrogen; 20% palladium hydroxide-activated charcoal / methanol; acetic acid / 18 h / 2585.81 Torr 4: potassium carbonate / N,N-dimethyl-formamide / 19 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: benzene / 8 h 2: 89 percent / H2 / Pd/C / ethyl acetate / 12 h / 2585.74 Torr | ||
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 °C 1.2: 1 h / 0 - 5 °C 2.1: sodium hydroxide; water / methanol / 2 h / 70 °C 2.2: 0.5 h / 4 °C / pH 2 3.1: hydrogen / palladium 10% on activated carbon / methanol / 0.25 h / 2068.65 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 95 percent / K, 18-crown-6, t-BuNH2 / diethyl ether 2: 51 percent / Li, EtNH2 / 6 h / 17 °C | ||
Multi-step reaction with 3 steps 1: N2H4*H2O 2: Py 3: Na2CO3 / 160 - 165 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In dichloromethane; for 1h; | An oven-dried 3-neck flask equipped with 125-mL addition funnel was charged with anhydrous CH2CI2 (150 mL) and anhydrous DMSO (10.3 mL, 0.145 mol, 2.5 equiv) under argon atmosphere and cooled TO-78C. Slow dropwise addition of oxalyl chloride (6.7 mL, 0.0768 mol, 1.32 equiv) followed by stirring for 15 min provided an activated DMSO adduct. This was treated with a solution of Step 2 compound (9.67 g, 58.2 mmol, 1 equiv) in dry CH2C12 (75 mL) and the reaction allowed to stir for 1 h. The resulting white mixture was then treated dropwise mixture was diluted with Et20 (400 mL) and the layers were separated. The organics were washed organic with cold 10% aq KH2PO4 (3X150 mL) and satd aq NaCI (100 mL). The organics were dried (NA2SO4), filtered and concentrated. The residue was purified by flash column chromatography on silica GEL (5X10 cm) with CH2CI2 to give the Step 3 compound as a white solid (9.40 g, 98%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With NaH In tetrahydrofuran; water | 17 3-(1-Adamantyl)-2-phenylpropenenitrile 3-(1-Adamantyl)-2-phenylpropenenitrile A solution of diethyl 1-cyano-1-phenylmethylphosphonate (10.97 g, 43.3 mmol) in dry THF (60 mL) at 0° C. was treated with NaH (60% dispersion in oil, 1.7 g, 43.3 mmol), stirred at 0° C. for 40 min, warmed to room temperature for 20 min, treated with a solution of 1-adamantanecarboxaldehyde (3.56 g, 21.7 mmol) in dry THF (10 mL) and heated at 60° C. for 16 h. The reaction mixture was cooled, treated with water (50 mL), extracted with EtOAc (3*20 mL), the extracts washed with brine (40 mL), dried (MgSO4) and concentrated in vacuo. The resulting brown oil was purified by chromatography [SiO2, heptane-EtOAc (9:1)] and recrystallized (heptane) to give the product (1.62 g, 28%) as a white solid: mp 107-108° C; IR νmax (Nujol)/cm-1 2924, 2852, 2218, 1497, 1448, 1377, 1343, 1101, 910, 762, 750 and 689; NMR δH (400 MHz, CDCl3) 1.76 (6H, m), 1.99 (6H, m), 2.07 (3H, m), 6.50 (1H, s), 7.37 (3H, m) and 7.51 (2H, m); Anal. Calcd for C19H21N: C, 86.65; H, 8.04; N, 5.32. Found: C, 86.58; H, 8.09; N, 5.33. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30.1% | With n-butyllithium In tetrahydrofuran; hexane; dichloromethane; water | 105 1-(1-Adamantyl)-2-(3-chlorophenyl)-2-(1-imidazolyl)-ethanol EXAMPLE 105 (COMPOUND 105) 1-(1-Adamantyl)-2-(3-chlorophenyl)-2-(1-imidazolyl)-ethanol 15.5 ml (23 mmol) of a 1.5 molar solution of n-butyllithium in hexane were added dropwise to a solution of 3.85 g (20 mmol) of N-(3-chlorobenzyl)-imidazole in 46 ml of absolute THF at -70° C. The mixture was stirred for 30 minutes at -70° C., after which a solution of 3.20 g (20 mmol) of 1-formyladamantane in 20 ml of absolute THF was added dropwise at -70° C. Stirring was continued for 1 hour at about -70° C. and for 2 hours at about -70° C. to room temperature, 120 ml of water were added at about 10° C., while cooling, and the suspension formed was stirred for 1.5 hours at 5°-8° C. Thereafter, the crystalline substance (crude product) was filtered off under suction and rinsed with water and hexane, and the crystalline product, dissolved in CH2 Cl2, was filtered over a silica gel/CH2 Cl2 column (diameter 2.0 cm, height 20 cm). The filtered solution was evaporated down in vacuo and the residue (2.36 g) was crystallized from acetone. 2.15 g (=30.1% yield) of pure 1-(1-adamantyl)-2-(3-chlorophenyl)-2-(1-imidazolyl)-ethanol of melting point 115° C. were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium carbonate; In methanol; at 20℃; for 4h; | EXAMPLE 32 Preparation of 1-Ethynyladamantane To a stirred mixture of adamantane-1-carbaldehyde (2.0 g, 12.2 mmol) and K2CO3 (3.36 g, 24.4 mmol) in methanol (200 ml) is added dimethyl (1-diazo-2-oxopropyl)phosphonate (2.8 g, 14.6 mmol) dropwise. After stirring for 4 h at room temperature, the reaction mixture is diluted with ether (100 ml). The mixture is washed with NaHCO3 solution (5% in water, 300 ml). The organic layer is separated, dried (MgSO4) and concentrated. The crude material is purified by chromatography (silica gel, 100% hexane) to afford the title compound 1.5 g (75%) as a white solid. mp: 80-82 C. MS (+) ES: 161 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With methane In dichloromethane reaction at 25°C for minutes; recrystn. (2x); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | In dichloromethane byproducts: CH4; Ir-complex was dissolved in CH2Cl2, ligand in CH2Cl2 was added over 1 min, mixt. was stirred at room temp. overnight under N2; volatiles were removed in vacuo, washed with Et2O, pentane was added; | |
63% | With methane In dichloromethane reaction at 25°C for minutes; recrystn. (2x); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-Adamantanecarbaldehyde With titanium(IV) isopropylate In dichloromethane at 0 - 20℃; for 0.25h; Stage #2: trimethylsilyl cyanide In dichloromethane at 20℃; for 6h; Stage #3: With hydrogenchloride In tetrahydrofuran; dichloromethane; water for 0.166667h; | 4a The aldehyde 702 (4.00 g, 24.3 mmol) was then dissolved in 30 mL of dry dichloromethane and to it was added Ti(OiPr)4 (4.21 mL, 12.2 mmol) at 00C, and the resulting mixture was stirred for 15 minutes at room temperature. Trimethylsilyl cyanide (TMSCN) (18.6 mL, 125 mmol) was added slowly, and the reaction stirred at room temperature for 6 h. After completion, a mixture of 1.5 N HCl and THF (1: 1, 30 mL each) was added to the reaction mixture and stirred for 10 min. Solvent was removed under reduced pressure, and the mixture was extracted with ethyl acetate (3 x 50 mL). The organic layer was dried over Na2SO4, and concentrated to afford Compound 703 (3.4 g). 1H NMR (200 MHz, CDCl3): δ 4.26 (d, IH); 2.43 (bs, IH); 2.10-1.60 (m, 15H). IR cm"1 (KBr) 3250, 2120. | |
In tetrahydrofuran at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 24h; | |
With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Stage #1: 1-Adamantanecarbaldehyde; L-histidine monohydrochloride With triethylamine In methanol at 20℃; for 5h; Stage #2: With palladium on carbon; hydrogen In methanol at 20℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | Stage #1: 1-Adamantanecarbaldehyde; L-tryptophan hydrochloride With triethylamine In methanol at 20℃; for 5h; Stage #2: With palladium on carbon; hydrogen In methanol at 20℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | Stage #1: 1-Adamantanecarbaldehyde; L-histidine hydrogen chloride With triethylamine In methanol at 20℃; for 5h; Stage #2: With palladium on carbon; hydrogen In methanol at 20℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: trimethyl phosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Stage #2: 1-Adamantanecarbaldehyde In tetrahydrofuran at 0 - 5℃; for 1h; | A suspension of NaH (2.38 g, 99 mmol) in THF (200 mL) was cooled to 0 °C and trimethylphosphonoacetate (12.89 g, 70.8 mmol) was added slowly at 0 °C, to give milky white solid. Resulting mixture was stirred for 15 minutes and adamantane-l- carbaldehyde (8.94 g, 54.5 mmol) in THF (100 mL) was added slowly at 0 °C. Reaction mixture was stirred at 5 °C for 1 h and the mixture was quenched with water (50 mL) and THF was distilled out. The sticky compound obtained was diluted with water (150 mL) and extracted with EtOAc (2 x 150 mL). EtOAc layer was dried over anhydrous Na2S04, distilled and dried to afford the crude product (10.75g, 91% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: ethyl (2E)-4-(diethoxyphosphoryl)crotonate With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Stage #2: 1-Adamantanecarbaldehyde In tetrahydrofuran at 0 - 5℃; for 1h; | A suspension of NaH (1.18 g, 49 mmol) in THF (50 mL) was cooled to 0 °C and triethyl-4-phosphonocrotonate (8.83 g, 35 mmol) was added slowly at 0 °C. The resulting mixture was stirred for 15 minutes and adamantane-l-carbaldehyde (4.46 g, 27 mmol) in THF (50 mL) was added slowly at 0 °C. Reaction mixture was stirred at 5 °C for 1 h. It was then quenched with water (10 mL) and THF was distilled out. The sticky compound obtained was diluted with water (150 mL) and extracted with EtOAc (2 x 150 mL). EtOAc layer was dried over anhydrous Na2S04, distilled and dried to afford the crude product (6.7 g, 95% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | General procedure: The aldehyde (1 mmol) and <strong>[59528-27-7]4-iodobenzylamine hydrochloride</strong> (0.270 g, 1 mmol) were mixed with dry DCE (25 mL). If indicated, TEA (139 muL, 1 mmol) was added to liberate the parent amine. Next, Na(AcO)3BH (0.318 g, 1.5 mmol) was added and the mixture was stirred at rt for 24-36 h. Aq NaOH-soln (2 M) was added and the mixture was stirred vigorously for 10 min, after which DCM was added. The organic layer was separated and the aq layer was back-extracted with DCM (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated. If required, the crude product was purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid In 1,2-dichloro-ethane at 20℃; for 18h; | General procedure for the synthesis of focused library of dipiperidines Step e. To each well was added 0.2 ml of a mixture DCE/AcOH (9/1, v/v), and solutions were transferred into the reactor block. To the solutions were added carbonyl compounds, 0.06 ml of appropriate stock solution, followed by an addition of resin bound trimethylammonium cyanoborohydride, 1 mg (4 μM/well) and mixture allowed to react for 18 h. At the end reaction mixture was filtered into collection plate and dried in SpeedVac. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid In 1,2-dichloro-ethane at 20℃; for 18h; | General procedure for the synthesis of focused library of dipiperidines Step e. To each well was added 0.2 ml of a mixture DCE/AcOH (9/1, v/v), and solutions were transferred into the reactor block. To the solutions were added carbonyl compounds, 0.06 ml of appropriate stock solution, followed by an addition of resin bound trimethylammonium cyanoborohydride, 1 mg (4 μM/well) and mixture allowed to react for 18 h. At the end reaction mixture was filtered into collection plate and dried in SpeedVac. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.013 g | With acetic acid In 1,2-dichloro-ethane at 20℃; for 18h; | General procedure for the synthesis of focused library of dipiperidines Step e. To each well was added 0.2 ml of a mixture DCE/AcOH (9/1, v/v), and solutions were transferred into the reactor block. To the solutions were added carbonyl compounds, 0.06 ml of appropriate stock solution, followed by an addition of resin bound trimethylammonium cyanoborohydride, 1 mg (4 μM/well) and mixture allowed to react for 18 h. At the end reaction mixture was filtered into collection plate and dried in SpeedVac. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; tris[3,5-bis(trifluoromethyl)phenyl]-borane; In 1,4-dioxane; at 100℃; for 12h;Glovebox; | General procedure: In a glovebox, aldehydes (0.25 mmol) and the Hantzsch ester 1 (95 mg, 0.38 mmol) were added to asolution of tris[3,5-bis(trifluoromethy)phenyl]borane (9) (8.1 mg, 12.5 mumol) in 1 mL of anhydrous1,4-dioxane. The reaction mixture was stirred at 25 or 100 C for 12 h. An internal standard (biphenylor mesitylene) was added to the reaction mixture and filtrated through a cotton plug. The resultingsolution was analyzed with gas chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogensulfite In methanol; water at 25 - 85℃; | 8 Example-8; Charge compound XV (100 gm) and water (2500 ml) to RBF at 25° to 35°C. Stir for 10 minutes, slowly charge NaHS03 (66 gm) into the reaction mass at 25° to35°C. Stir for 10 minutes, slowly add sodium cyanide (33 gm) into the reaction mass at 25° to 35°C. Stir for 20 minutes at 25° to 35°C. Add (S)-(+)-p-toluenesulfinamide (104 gm) to the reaction mass at 25° to 35°C. Charge methanol (500 ml) to the reaction at 25° to 35°C. Maintain the reaction mass for 1-2 hrs at 25° to 35°C. Slowly raise the reaction mass temperature to 80° to 85°C. Maintain reaction mass for 18 to 20 hrs at 80° to 85°C. Check TLC for compliance. Cool the reaction mass to 25° to35°C. Charge ethyl acetate (1750 ml) to the reaction mass at 25° to35°C. Stir for 10 minutes. Separate the layers. Extract aqueous layer with ethyl acetate at 25° to 35°C. Wash ethyl acetate layer with 10% potassium permanganate solution (500ml x 2). Distill out ethyl acetate completely under vacuum at or below 50°C. Residue weight: 130 gm. (Compound XVI). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With trifluoroacetic acid In dichloromethane at 20℃; for 168h; Inert atmosphere; | 5 4.2. General procedure for preparation of receptors 1-4, 7 and 8 General procedure: In a two-neck flask under a stream of nitrogen carbaldehyde 10 or ketone 11 (1 mmol) and the corresponding phenylpyrroles 9a-c (2 mmol) were dissolved in a small volume of dry CH2Cl2 (ca. 5-10 mL). By use of a syringe, to the reaction mixture was added TFA (0.1 mmol) and the mixturewas stirred at rt, while the progress of the reactionwas followed by TLC using CH2Cl2 as an eluent. Upon the disappearance of the starting 2-phenylpyrrole, the reactionwas quenched by the addition of an aqueous solution of NaOH (0.1 M, w20 mL) and the layers were separated. The aqueous layer was extracted two more times using CH2Cl2 (2 20 mL), the organic extracts were washed with water (20 mL), collected and dried over anhydrous MgSO4. After filtration, the solvent was evaporated on a rotary evaporator and the obtained dark residue was purified by chromatography, crystallization or washing with solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With trifluoroacetic acid In dichloromethane at 20℃; for 96h; Inert atmosphere; | 2 4.2. General procedure for preparation of receptors 1-4, 7 and 8 General procedure: In a two-neck flask under a stream of nitrogen carbaldehyde 10 or ketone 11 (1 mmol) and the corresponding phenylpyrroles 9a-c (2 mmol) were dissolved in a small volume of dry CH2Cl2 (ca. 5-10 mL). By use of a syringe, to the reaction mixture was added TFA (0.1 mmol) and the mixturewas stirred at rt, while the progress of the reactionwas followed by TLC using CH2Cl2 as an eluent. Upon the disappearance of the starting 2-phenylpyrrole, the reactionwas quenched by the addition of an aqueous solution of NaOH (0.1 M, w20 mL) and the layers were separated. The aqueous layer was extracted two more times using CH2Cl2 (2 20 mL), the organic extracts were washed with water (20 mL), collected and dried over anhydrous MgSO4. After filtration, the solvent was evaporated on a rotary evaporator and the obtained dark residue was purified by chromatography, crystallization or washing with solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With trifluoroacetic acid In dichloromethane at 20℃; for 144h; Inert atmosphere; | 2 4.2. General procedure for preparation of receptors 1-4, 7 and 8 General procedure: In a two-neck flask under a stream of nitrogen carbaldehyde 10 or ketone 11 (1 mmol) and the corresponding phenylpyrroles 9a-c (2 mmol) were dissolved in a small volume of dry CH2Cl2 (ca. 5-10 mL). By use of a syringe, to the reaction mixture was added TFA (0.1 mmol) and the mixturewas stirred at rt, while the progress of the reactionwas followed by TLC using CH2Cl2 as an eluent. Upon the disappearance of the starting 2-phenylpyrrole, the reactionwas quenched by the addition of an aqueous solution of NaOH (0.1 M, w20 mL) and the layers were separated. The aqueous layer was extracted two more times using CH2Cl2 (2 20 mL), the organic extracts were washed with water (20 mL), collected and dried over anhydrous MgSO4. After filtration, the solvent was evaporated on a rotary evaporator and the obtained dark residue was purified by chromatography, crystallization or washing with solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-Adamantanecarbaldehyde; histamine With sodium cyanoborohydride In methanol at 20℃; Inert atmosphere; Stage #2: methanesulfonic acid In diethyl ether at 0℃; for 0.25h; Inert atmosphere; | 7a Procedure A: Amine (1.2 equiv) and aldehyde/ketone (1.0 equiv) were mixed in methanol and then treated with sodium cyanoborohydride (3.0eq). The mixture was stirred at room temperature under a N2 atmosphere overnight. The reaction mixture was quenched by adding water, and the product was extracted with butanol. The combined organic layer was dried over Na2SC"4, and concentrated under reduced pressure. The crude product was separated by flash column chromatography (1-10% CH30H/CH2C12).; Based on general procedure A, from adamantan-l-ylamine and 4-(tert-butyl)benzaldehyde. The pure free amine was dissolved in Et20 and cooled to 0 °C and MeS03H (1 equiv) was added under N2 and then mixture was stirred at 0 °C for 15 min and filtered to give a white solid. Data: LC/MS (ESCi) m/z 298.25 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium cyanoborohydride In methanol at 20℃; Inert atmosphere; | 1 General procedure: Procedure A: Amine (1.2 equiv) and aldehyde/ketone (1.0 equiv) were mixed in methanol and then treated with sodium cyanoborohydride (3.0eq). The mixture was stirred at room temperature under a N2 atmosphere overnight. The reaction mixture was quenched by adding water, and the product was extracted with butanol. The combined organic layer was dried over Na2SC"4, and concentrated under reduced pressure. The crude product was separated by flash column chromatography (1-10% CH30H/CH2C12). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 1.16667h; Inert atmosphere; Overall yield = 63.0 %; Overall yield = 4.7 mg; | 1.3 (3) Synthesis of 25-(1-Adamantyl)-1α,25-dihydroxy-2-methylene-23,23,24,24-tetradehydro-19,26,27-trinorvitamin D3 1,3-bis-(tert-butyldimethylsilyl) ether (3) [0048] To a solution of acetylene form 2b (6.1 mg, 0.010 mmol) in THF (200 µL), a solution of n-butyllithium in hexane (19.2 µL, 1.6 M, 0.050 mmol, 5 eq) was added in argon at 0°C under stirring. After stirring for 10 min, a solution of 1-formyladamantane (4.92 mg, 0.030 mmol, 3 eq) in THF (70 µL) was added slowly to the reaction mixture, followed by stirring at 0°C for 1 hr. Saturated ammonium chloride was added to the reaction solution at 0°C, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by silica gel column chromatography (1.2 g) to obtain alcohol form 3 (4.7 mg, 63.0%) as a 1:1 mixture of 25-epimers from 1% ethyl acetate/hexane elution part. This mixture was separated by normal phase HPLC [Hibar RT LiChrosorb Si 60 (7 µm) 10 mm x 250 mm; CH2Cl2/hexane, 2/3, 4.0 mL/min] to obtain a less polar (25R) form (3b) and a more polar (25S) form (3a). 3: 1HNMR (CDCl3, δ) 0.02, 0.05, 0.07, 0.08 (each 3H, s), 0.56 (3H, s), 0.86, 0.90 (each 9H, s), 1.06-1.12 (3H, m), 2.15-2.20 (1H, m), 2.29-2.38 (3H, m), 2.45-2.54 (2H, m), 3.89 (1H, s), 4.41-4.45 (2H, m), 4.92 (1H, s), 4.97 (1H, s), 5.84 (1H, d, J = 11.2 Hz), 6.21 (1H, d, J = 11.2 Hz). MS m/z (%): 746 (M+, 2), 614 (18), 596 (20), 366 (20), 234 (12), 135 (100), 73 (80). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.5% | With n-butyllithium In tetrahydrofuran at 0℃; for 1.16667h; | 4.9 (9) Synthesis of Adamantane Compound 17 [0070] A solution of the acetylene form 16 (11.7 mg, .02071 mmol) in anhydrous tetrahydrofuran (414 µL) was cooled to 0°C. To this solution, n-butyllithium (65 µL, 0.104 mmol, 5 eq.) was added. After stirring for 10 min at the same temerature, a solution of 1-formyl adamantane (15.4 mg, 0.0938 mmol, 4.5 eq.) in anhydrous tetrahydrofuran (220 µL) was added dropwise. The mixture was stirred at the same temperature for 1 hr. Saturated aqueous ammonium chloride solution was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography (SiO2, 2 g) to obtain adamantine compound 17 (10.8 mg, 71.5%) from 3% ethyl acetate/hexane elution part. 17 1H-NMR (CDCl3 δ: 0.02, 0.05, 0.06, 0.08 (each 3 H, s, SiMe×4), 0.68 (3 H, s, -CH3), 0.86, 0.90 (each 9 H, s, t-Bu), 2.09 (1 H, m), 2.18 (1 H, dd, J= 12.4, 8.4 Hz), 2.30 (1 H, m), 2.47 (3 H, m), 2.85 (1 H, m), 3.00 (1 H, m), 3.92 (1 H, d), 4.43 (1 H, m), 4.92, 4.98 (each 1 H, m), 5.84 (1 H, d, J =11.2 Hz), 6.20 (1 H, d, J =11.2 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With sodium hydrogensulfite at 0 - 60℃; | |
287 g | With sodium hydrogensulfite In methanol; water at 0 - 55℃; | 3 Oxidation of the adamantane-1-methanol (compound-II) to corresponding aldehyde and hydrolysis of the nitrile to corresponding 2-adamantane-2(R)-2-hydroxy-2- phenylethyl amino acetic acid (compound-III) 200 g, (1.217M) of the semi solid Step-A aldehyde compound obtained from the above step was suspended, in 2.5L of water and mixture was cooled to 0-5°C. The mixture was treated with 140. Og (1.66M) of NaHS03 and 1 10.0 g ( 1.692M) of NaCN and a solution of (R)-phenyl glycinol in methanol (200 g,1.457M dissolved in 1600mL of methanol). The resulting mixture was stirred at 0-5°C for 10-15min, then heated to 25-30°C and maintained for 1-2 hrs. Again the temperature was raised to 50-55°C and maintained for 4-5 hours at 50 - 55° C. When reaction was completed, reaction mass was cooled to 40-45°C, and 1000 mL of ethyl acetate was charged and mixed. After mixing for 15minutes, the layers were separated. The aqueous fraction was extracted with 500mL of ethyl acetate. The combined ethyl acetate layer was washed with l OOOmL saturated sodium chloride solution and dried over anhydrous Na2S04. Combined organic layer was concentrated under vacuum at below 50°C and 287 g of the desired Step-B nitrile compound having HPLC purity above 95 % was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With <i>L</i>-proline In chloroform at 30℃; enantioselective reaction; | General Procedure for the (S)-Proline Catalyzed Aldol Reaction of Acetone with α-Trisubstituted Aliphatic Aldehydes General procedure: (S)-proline (23 mg, 0.20 mmol, 0.20 equiv) was added to a solution of aldehyde (1 mmol, 1 equiv) indry acetone (4 mL) and dry chloroform (1 mL) and was stirred at 30 °C. After this time the mixturewas diluted with water (5 mL) and diethyl ether (5 mL) and partitioned. The aqueous layer was washed with diethyl ether (5 mL x 3), and the combined organic layers were dried over Na2SO4. Evaporation of the solvent and flash column chromatography with the specified solvent system afforded the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With rac-Pro-OH In chloroform at 30℃; | General Procedure for the (S)-Proline Catalyzed Aldol Reaction of Acetone with α-Trisubstituted Aliphatic Aldehydes General procedure: (S)-proline (23 mg, 0.20 mmol, 0.20 equiv) was added to a solution of aldehyde (1 mmol, 1 equiv) indry acetone (4 mL) and dry chloroform (1 mL) and was stirred at 30 °C. After this time the mixturewas diluted with water (5 mL) and diethyl ether (5 mL) and partitioned. The aqueous layer was washed with diethyl ether (5 mL x 3), and the combined organic layers were dried over Na2SO4. Evaporation of the solvent and flash column chromatography with the specified solvent system afforded the desired products. Racemates All racemates were prepared following the same general procedure for the asymmetric reaction, usingrac-proline as catalyst. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With piperidine In methanol at 100℃; for 0.166667h; | 4.1.4 General procedure II General procedure: Condensation of 2-p-tolylthiazol-4(5H)-one with a corresponding aldehyde. A suspension of 2-p-tolylthiazol-4(5H)-one, 3, (1 eq), aldehyde (1 eq), 1-2 drops piperidine in methanol was heated in the microwave to 90-100°C for 3-20min. The product was either directly isolated by collection of the precipitate or the solvent was removed under reduced pressure and the residue was recrystallized. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium hexafluorophosphate; tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen; 1,1,1,3,3,3-hexamethyl-disilazane In acetonitrile at 30℃; for 8h; Sealed tube; | 10 Example 10: Preparation of 1-adamantanecarbonitrile (formula (2-3)) In a 100 ml flask, 50 mL of acetonitrile, 10 mmol of HMDS, 0.4 mmol of TEMPO, 0.4 mmol of KPF6, and 0.6 mmol of TBN were charged. The air in the bottle was replaced with oxygen. After sealing the bottle with a rubber stopper, an oxygen balloon was inserted, Heated to 25 ° C in a preheated water bath, and 4 mmol of 1-adamantane formaldehyde (as in the formula (1-3)) was added and reacted for 12 h. The reaction solution was stirred with sodium thiosulfate solution and extracted with ether. The organic layer was separated, the solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography to give a mixture of ethyl acetate and petroleum ether in a volume ratio of 1: 100 Eluting solvent containing the target compound was collected, and the solvent was distilled off to give 1-adamantanecarbonitrile, and the isolation yield was 85%.; The reaction was carried out in the same manner as in Example 9 except that the reaction temperature was 30 ° C, the reaction time was 8 hours, the isolation yield of 1-adamantanecarbonitrile was 97% |
95% | With potassium hexafluorophosphate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen; 1,1,1,3,3,3-hexamethyl-disilazane; sodium nitrite In acetic acid; acetonitrile at 30℃; for 4h; Sealed tube; | |
95% | With tert.-butylhydroperoxide; ammonium acetate; iodine; sodium carbonate In ethanol at 50℃; for 5h; Green chemistry; |
95% | With tert.-butylhydroperoxide; ammonium acetate; iodine; sodium carbonate In ethanol at 50℃; for 5h; | 36 Example 36: Preparation of 1-adamantane carbonitrile (Formula (2-21)) In a 25 mL two-necked round bottom flask equipped with a thermometer and a magnetic stirrer4mmol1-adamantaneformaldehyde(formula (1-21)), 6 mmol of NH4OAc, 4 mmol of Na2CO3, 4.4 mmol of TBHP, 0.1 mmol of I2, 5 mL of anhydrous ethanol And the reaction flask was then placed in an oil bath preheated to 50 ° C and the magnetic stirrer was opened for 5 h. Reaction solution Adding sodium thiosulfate solution and stirring, then extracting with ether, separating the organic layer, distilling off the solvent under reduced pressure, and then performing column chromatography The eluent was taken as a mixture of ethyl acetate / petroleum ether in a volume ratio of 1: 100 as the eluent, and the eluate containing the title compound was collected. In addition to solvent that 1-adamantane carbonitrile, the separation yield of 95%. |
94% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium perchlorate; acetic acid; lithium hexamethyldisilazane In acetonitrile for 10h; Electrochemical reaction; | General procedure: Preparative electrolysis experiments were performed using 263 APotentiostat/Galvanostat (Princeton Applied Research, USA). 0.1 MNaClO4-CH3CN solution (10 mL) containing aldehydes (1 mmol),TEMPO (0.1 mmol), HMDS (2.5mmol) and AcOH (2.5mmol) was electrolyzedwith stirring in an undivided cell (30 mL) equipped with twoplatinum sheets as anode (1.5 cm2) and cathode (3.0 cm2) respectivelyat a constant potential of 1.5 V vs Ag/Ag+ (0.1MAgNO3 in acetonitrile).The electrode separation was 1 cm. When the reaction was finished,10mL of saturatedNa2SO3 solution was added into the reactionmixtureand stirred for 15 min. Then the mixture was extracted with CH2Cl2(20 mL × 3). The organic layer was dried with anhydrous Na2SO4 andconcentrated in a rotary evaporator. The productswere obtained via purificationof column chromatography and their structures were confirmedby 1H NMR, 13C NMR and MS. NMR was performed on a BrukerAvance III spectrometer. GC-MS was performed on the Thermo TraceISQ instrument with TG 5MS capillary column. |
86% | With ammonium acetate; acetic acid; N-(2,2,6,6-tetramethyl-1-oxopiperidin-1-ium-4-yl)acetamide tetrafluoroborate at 70℃; for 12h; Inert atmosphere; | General procedures for 4-AcNH-TEMPO+BF4- mediated nitriles synthesis General procedure: A 15 mm flame-dried test tube, which was equipped with a magnetic stir bar and charged with aldehyde (0.3 mmol, in case of solid), 4-AcNH-TEMPO+BF4- (2.0 equiv, 0.6 mmol), and NH4OAc (4.0 equiv, 1.2 mmol), was evacuated and backfilled with nitrogen (this process was repeated 3 times). After 0.3 mL of AcOH was added, aldehyde (0.3 mmol, in case of liquid), and AcOH (0.3 mL) were added in sequence. The reaction mixture was stirred for 12 h at 70 oC under N2 balloon, and then cooled to room temperature. The reaction was diluted by adding EtOAc and washed 4 M HCl aqueous solution. Two layers were separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with Na2CO3 aqueous solution. The organic layer was dried over MgSO4, filtered, and concentrated to a volume of approximately 20 mL by evaporator. To eliminate remaining aldehyde, aqueous 2 M Na2S2O5 aqueous solution (20 mL) was added to the organic layer and stirred for 2 hours. Two layers were separated, and the organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography to give nitrile products. |
82% | Stage #1: 1-Adamantanecarbaldehyde With pyridine; 1,1,1,3,3,3-hexamethyl-disilazane In dichloromethane at 26℃; for 0.0833333h; Stage #2: With N-(2,2,6,6-tetramethyl-1-oxopiperidin-1-ium-4-yl)acetamide tetrafluoroborate In dichloromethane at 26℃; for 18h; | |
75% | With dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](benzylidene) (tricyclohexylphosphine) ruthenium(II); ammonium acetate; oxygen In 5,5-dimethyl-1,3-cyclohexadiene at 130℃; for 1.5h; Sealed tube; | |
Multi-step reaction with 2 steps 1: pyridine / dichloromethane / 0.08 h / 20 °C 2: N-(2,2,6,6-tetramethyl-1-oxopiperidin-1-ium-4-yl)acetamide tetrafluoroborate / dichloromethane / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: diethyl (trichloromethyl)phosphonate With n-butyllithium In tetrahydrofuran; hexane at -100 - -90℃; for 0.25h; Inert atmosphere; Stage #2: 1-Adamantanecarbaldehyde In tetrahydrofuran; hexane at -90 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 1-acetoxy-1,2-benziodoxol-3-one; [Ir(2-(2,4-difluorophenyl)-4-(trifluoromethyl)pyridine)2(5,5'-bis(trifluoromethyl)-2,2'-bipyridine)]PF6; sodium ortho-iodobenzoate In 1,2-dichloro-ethane at 20℃; for 24h; Inert atmosphere; Irradiation; | |
47% | With tert.-butylhydroperoxide In water; acetonitrile at 85℃; for 24h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | General procedure: To a cooled (0 C) solution of the alcohol (1 mmol) in CH2Cl2 (2 mL) were added successively TEMPO (7.8 mg, 5 mol%), TCCA (278 mg, 1.2 equiv) in portions and the suspension was stirred until the consumption of the alcohol (progress of the reaction was monitored by TLC). In the case of substrates 2g,j-n, NaHCO3 (8 equiv) was added before the addition of TCCA. HFIP alcohol (210 muL, 2 equiv) and pyridine (320 muL, 4 equiv) were then successively added dropwise at 0 C. After warming, the solution was stirred at r.t. until consumption of the aldehyde (for substrates 1j-n, the oxidative esterification was conducted at 0 C). The yellow suspension was poured onto a small column of silica gel and the HFIP ester was eluted with petroleum ether or a mixture of petroleumether-Et2O. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium hydrogensulfite In methanol; water at 0 - 20℃; for 18h; Reflux; | |
65% | With sodium hydrogensulfite In methanol; water at 0 - 20℃; for 18h; Reflux; | 58.4 Step 4 Step 3 compound (9.40 g, 57 mmol, 1 equiv) was suspended in H2O (145 mL) and cooled to 0°C. The mixture was treated with NaHSO3 (5.95 g, 57 mmol, 1 equiv), KCN (4.0 g, 59 mmol, 1.04 equiv), and a solution of (R)-(-)-phenylglycinol (8.01 g, 57 mmol, 1 equiv) in MeOH (55 mL). The resulting mixture was stirred at rt for 2 h, then refluxed for 16 h. The mixture was cooled to rt, and 200 mL of EtOAc added. After mixing for 15 min the layers were separated. The aqueous fraction was extracted with EtOAc. The combined EtOAc extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered and the filtrate concentrated. The product was purified by flash column chromatography on silica gel (6.4x20 cm) with 20% EtOAc/hexanes to give the desired (R,S) product as a white solid (11.6 g, 37.4 mmol, 65%): MS m/e 311 (M+H)+. |
41.45% | With sodium hydrogensulfite In methanol; water at 0 - 90℃; for 8h; | Step 2. Preparation of (2S)-2-(1-adamantyl)-2-[[(1R)-2-hydroxy-1-phenyl- ethyl]amino]acetonitrile To a solution of adamantane-1-carbaldehyde (140 g, 0.85mol) in H2O (1.5 L) was added NaHSO3 (88.7 g, 0.85mol, 60 mL) and KCN (57.2 g, 0.88 mol) at 0 °C, then (2R)-2-amino-2- phenyl-ethanol (119 g, 0.87 mol) in MeOH (500 mL) was added dropwise into the yellow suspension at 0 °C, then the yellow suspension was stirred at 0 °C for 1h. The yellow suspension was heated to 90 °C and stirred for 7h. TLC (petroleum ether : ethyl acetate = 3:1, Rf = 0.31) showed the reaction was complete. The yellow suspension was cooled to 25 °C and extracted with ethyl acetate (2 L x 3). The combined organic phase was washed with brine (1 L), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The solution of MTBE (1 L) was added to the yellow solid and stirred for 30 min. Then the mixture was filtered and the cake was dried in vacuum to give (2S)-2-(1-adamantyl)-2-[[(1R)-2-hydroxy-1-phenyl- ethyl]amino]acetonitrile (330 g, 1.06 mol, 41.45% yield) as a white solid. TLC (petroleum ether : ethyl acetate = 3:1, Rf = 0.31) 1H NMR: 400 MHz CDCl3 δ7.35-7.24 (m, 5H), 4.07-4.03 (m, 1H), 3.79-3.76 (m, 1H), 3.57-3.52 (m, 1H), 2.86 (s, 1H), 2.20 (s, 1H), 2.02 (s, 3H), 1.76-1.55 (m, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; | |
73% | With titanium(IV) isopropylate at 70℃; for 18h; Inert atmosphere; | |
With titanium(IV) isopropylate In tetrahydrofuran at 60℃; Inert atmosphere; | 4.2 General procedure for the preparation of imines N1-187,8 General procedure: A round bottom flask was charged with a solution of chiral tert-butanesulfinamide (11 mmol) and aldehyde (10 mmol) in THF (20 mL) followed by the addition of isopropyl titanate (15 mmol). The reaction mixture was stirred until completion of aldehyde as indicated by TLC. The reaction was then quenched with water, diluted with EtOAc and dried over MgSO4. The solvent was removed in vacuo and the crude product was purified by silica gel column chromatography using Petroleum Ether/AcOEt as an eluent to give the desired product in 58-95% yields. |
With caesium carbonate In dichloromethane at 45℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With potassium triethylborohydride In tetrahydrofuran at 50℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 86 %Spectr. 2: 12 %Spectr. | Stage #1: N-isopropyladamantane-1-carboxamide With 2-fluoropyridine; trifluoromethylsulfonic anhydride In dichloromethane at 0℃; for 0.333333h; Inert atmosphere; Stage #2: With 1,1,3,3-Tetramethyldisiloxane In dichloromethane at 0 - 20℃; for 6.16667h; Inert atmosphere; | 2.1.1 General procedure for reduction of secondary amidesto aldimines (general procedure A) General procedure: Into a solution of an amide (1.0 mmol) in 4 mL of anhydrous dichloromethane was added 2-fluoropyridine (117mg,103 μL, 1.2 mmol). After being cooled to 0 °C, trifluoromethanesulfonicanhydride (Tf2O) (310 mg, 185 μL, 1.1mmol) was added dropwise via a syringe and the mixturewas stirred for 20 min. To the resulting mixture, 1,1,3,3-tetramethyldisiloxane (TMDS) (94 mg, 124 μL, 0.7 mmol)was added dropwise and the resulting mixture was stirredfor 10 min at 0 °C. The mixture was allowed warming up toroom temperature and stirred for 6 h.Quenching with NaHCO3 (sat.): the reaction wasquenched by addition of 0.5 mL of a saturated aqueous solutionof sodium bicarbonate (NaHCO3) and diluted with 30mL of dichloromethane. Then 1,3,5-trimethoxybenzene(168.2 mg, 1.0 mmol) was added as internal standard. Thebiphasic mixture was transferred to a separation funnel andthe layers were separated. The aqueous layer was extractedwith dichloromethane (5 mL×2). The combined organiclayers were dried over anhydrous sodium sulphate(Na2SO4), filtered, and concentrated under reduced pressure.Yields of crude imines were calculated by integration of 1HNMR spectra.Quenching with NaH: the solvent was removed through adrying tube charged with anhydrous CaCl2 under reducedpressure, then 4 mL of THF and NaH (60 mg, 2.5 mmol,60% dispersion on mineral oil) were added. The resultingsuspension was stirred at r.t. for 20 min. Then 1,3,5-trimethoxybenzene (168.2 mg, 1.0 mmol) was added asinternal standard. Yields of crude imines were calculated byintegration of 1H NMR spectra. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With Wilkinson's catalyst; hydrogen In tetrahydrofuran at 25℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In ethyl acetate at 0 - 20℃; for 2h; | 4-Chloromethyl-5-methyl-2-(2,4,6-trimethylphenyl)oxazole(21c) To a solution of mesitylaldehyde (15.8 g, 416 mmol)in AcOEt (40 mL) was added 19 (10 g, 98.9 mmol) and HCl gaswas bubbled through the solution at 0°C for 0.5 h. The mixturewas stirred at the same temperature for 1.5 h. To the reactionmixture was added i-Pr2O and precipitated crystals were collectedby filtration to give a crude 20c (13.8 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With titanium(IV) tetraethanolate In tetrahydrofuran at 60℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With titanium(IV) isopropylate; sodium tetrahydroborate In ethanol at 20℃; for 2h; | Reductive amination of adamantane-1-carbaldehyde (3) using the NaBH4-Ti(OCHMe2)4 system (general procedure A). General procedure: A solution of aldehyde 3 (16.4 g, 0.1 mol), arylamine (0.12 mol), and Ti(OCHMe2)4 (59 mL, 56.6 g, 0.2 mol) in anhydrous EtOH (200 mL) was stirred for 8 h at room temperature, after addition of NaBH4 (5.7 g, 0.15 mol), the mixture was stirred for another 2 h and allowed to stand for ~12 h at room temperature. Then, the reaction mixture was treated with 2 M solution of NH4OH (300 mL), stirred for 20 min at room temperature, diluted with tert-butyl methyl ether (200 mL), and filtered, aqueous and organic phases were separated. A precipitate on the filter was washed with tert-butyl methyl ether (2x200 mL) and extracted the aqueous phase with this filtrate. The combined organic extracts were dried with anhydrous K2CO3, filtered, and concentrated on a water bath first at normal, then at reduced pressure. The residue was purified by recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With formic acid at 60 - 70℃; for 0.333333h; | Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). General procedure: Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). A mixture of adamantane-1-carbaldehyde (3) (16.4 g, 0.1 mol), arylamine (0.12 mol), and anhydrous formic acid (15 mL, 18.4 g, 0.4 mol) was heated to 60-70 °C for 20 min with stirring. After carbon dioxide ceased to evolve, the reaction mixture was treated with 6 M aqueous solution of HCl (40 mL) and refluxed 30 min with a reflux condenser, cooled to 10-15 °C, and filtered. A precipitate of the target product hydrochloride was stirred with 5% aqueous NaOH (50 mL) for 15 min at 40-50 °C. The free base was extracted with tert-butyl methyl ether (3x200 mL), the organic phase was dried with anhydrous K2CO3, filtered, and concentrated on a water bath first at normal, then at reduced pressure. The residue was purified by recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-Adamantanecarbaldehyde; <i>p</i>-toluidine With formic acid at 60 - 70℃; for 0.166667h; Stage #2: With hydrogenchloride In water for 0.5h; Reflux; | Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). General procedure: Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). A mixture of adamantane-1-carbaldehyde (3) (16.4 g, 0.1 mol), arylamine (0.12 mol), and anhydrous formic acid (15 mL, 18.4 g, 0.4 mol) was heated to 60-70 °C for 20 min with stirring. After carbon dioxide ceased to evolve, the reaction mixture was treated with 6 M aqueous solution of HCl (40 mL) and refluxed 30 min with a reflux condenser, cooled to 10-15 °C, and filtered. A precipitate of the target product hydrochloride was stirred with 5% aqueous NaOH (50 mL) for 15 min at 40-50 °C. The free base was extracted with tert-butyl methyl ether (3x200 mL), the organic phase was dried with anhydrous K2CO3, filtered, and concentrated on a water bath first at normal, then at reduced pressure. The residue was purified by recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With formic acid at 60 - 70℃; for 0.333333h; | Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). General procedure: Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). A mixture of adamantane-1-carbaldehyde (3) (16.4 g, 0.1 mol), arylamine (0.12 mol), and anhydrous formic acid (15 mL, 18.4 g, 0.4 mol) was heated to 60-70 °C for 20 min with stirring. After carbon dioxide ceased to evolve, the reaction mixture was treated with 6 M aqueous solution of HCl (40 mL) and refluxed 30 min with a reflux condenser, cooled to 10-15 °C, and filtered. A precipitate of the target product hydrochloride was stirred with 5% aqueous NaOH (50 mL) for 15 min at 40-50 °C. The free base was extracted with tert-butyl methyl ether (3x200 mL), the organic phase was dried with anhydrous K2CO3, filtered, and concentrated on a water bath first at normal, then at reduced pressure. The residue was purified by recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-Adamantanecarbaldehyde; p-aminoiodobenzene With formic acid at 60 - 70℃; for 0.166667h; Stage #2: With hydrogenchloride In water for 0.5h; Reflux; | Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). General procedure: Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). A mixture of adamantane-1-carbaldehyde (3) (16.4 g, 0.1 mol), arylamine (0.12 mol), and anhydrous formic acid (15 mL, 18.4 g, 0.4 mol) was heated to 60-70 °C for 20 min with stirring. After carbon dioxide ceased to evolve, the reaction mixture was treated with 6 M aqueous solution of HCl (40 mL) and refluxed 30 min with a reflux condenser, cooled to 10-15 °C, and filtered. A precipitate of the target product hydrochloride was stirred with 5% aqueous NaOH (50 mL) for 15 min at 40-50 °C. The free base was extracted with tert-butyl methyl ether (3x200 mL), the organic phase was dried with anhydrous K2CO3, filtered, and concentrated on a water bath first at normal, then at reduced pressure. The residue was purified by recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With titanium(IV) isopropylate; sodium tetrahydroborate In ethanol at 20℃; for 2h; | Reductive amination of adamantane-1-carbaldehyde (3) using the NaBH4-Ti(OCHMe2)4 system (general procedure A). General procedure: A solution of aldehyde 3 (16.4 g, 0.1 mol), arylamine (0.12 mol), and Ti(OCHMe2)4 (59 mL, 56.6 g, 0.2 mol) in anhydrous EtOH (200 mL) was stirred for 8 h at room temperature, after addition of NaBH4 (5.7 g, 0.15 mol), the mixture was stirred for another 2 h and allowed to stand for ~12 h at room temperature. Then, the reaction mixture was treated with 2 M solution of NH4OH (300 mL), stirred for 20 min at room temperature, diluted with tert-butyl methyl ether (200 mL), and filtered, aqueous and organic phases were separated. A precipitate on the filter was washed with tert-butyl methyl ether (2x200 mL) and extracted the aqueous phase with this filtrate. The combined organic extracts were dried with anhydrous K2CO3, filtered, and concentrated on a water bath first at normal, then at reduced pressure. The residue was purified by recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-Adamantanecarbaldehyde; 4-amino-phenol With formic acid at 60 - 70℃; for 0.166667h; Stage #2: With hydrogenchloride In water for 0.5h; Reflux; | Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). General procedure: Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). A mixture of adamantane-1-carbaldehyde (3) (16.4 g, 0.1 mol), arylamine (0.12 mol), and anhydrous formic acid (15 mL, 18.4 g, 0.4 mol) was heated to 60-70 °C for 20 min with stirring. After carbon dioxide ceased to evolve, the reaction mixture was treated with 6 M aqueous solution of HCl (40 mL) and refluxed 30 min with a reflux condenser, cooled to 10-15 °C, and filtered. A precipitate of the target product hydrochloride was stirred with 5% aqueous NaOH (50 mL) for 15 min at 40-50 °C. The free base was extracted with tert-butyl methyl ether (3x200 mL), the organic phase was dried with anhydrous K2CO3, filtered, and concentrated on a water bath first at normal, then at reduced pressure. The residue was purified by recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With formic acid at 60 - 70℃; for 0.333333h; | Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). General procedure: Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). A mixture of adamantane-1-carbaldehyde (3) (16.4 g, 0.1 mol), arylamine (0.12 mol), and anhydrous formic acid (15 mL, 18.4 g, 0.4 mol) was heated to 60-70 °C for 20 min with stirring. After carbon dioxide ceased to evolve, the reaction mixture was treated with 6 M aqueous solution of HCl (40 mL) and refluxed 30 min with a reflux condenser, cooled to 10-15 °C, and filtered. A precipitate of the target product hydrochloride was stirred with 5% aqueous NaOH (50 mL) for 15 min at 40-50 °C. The free base was extracted with tert-butyl methyl ether (3x200 mL), the organic phase was dried with anhydrous K2CO3, filtered, and concentrated on a water bath first at normal, then at reduced pressure. The residue was purified by recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-Adamantanecarbaldehyde; 4-nitro-aniline With formic acid at 60 - 70℃; for 0.166667h; Stage #2: With hydrogenchloride In water for 0.5h; Reflux; | Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). General procedure: Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). A mixture of adamantane-1-carbaldehyde (3) (16.4 g, 0.1 mol), arylamine (0.12 mol), and anhydrous formic acid (15 mL, 18.4 g, 0.4 mol) was heated to 60-70 °C for 20 min with stirring. After carbon dioxide ceased to evolve, the reaction mixture was treated with 6 M aqueous solution of HCl (40 mL) and refluxed 30 min with a reflux condenser, cooled to 10-15 °C, and filtered. A precipitate of the target product hydrochloride was stirred with 5% aqueous NaOH (50 mL) for 15 min at 40-50 °C. The free base was extracted with tert-butyl methyl ether (3x200 mL), the organic phase was dried with anhydrous K2CO3, filtered, and concentrated on a water bath first at normal, then at reduced pressure. The residue was purified by recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With formic acid at 60 - 70℃; for 0.333333h; | Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). General procedure: Reductive amination of adamantane-1-carbaldehyde (3) using Leuckart-Wallach reaction (general procedure B). A mixture of adamantane-1-carbaldehyde (3) (16.4 g, 0.1 mol), arylamine (0.12 mol), and anhydrous formic acid (15 mL, 18.4 g, 0.4 mol) was heated to 60-70 °C for 20 min with stirring. After carbon dioxide ceased to evolve, the reaction mixture was treated with 6 M aqueous solution of HCl (40 mL) and refluxed 30 min with a reflux condenser, cooled to 10-15 °C, and filtered. A precipitate of the target product hydrochloride was stirred with 5% aqueous NaOH (50 mL) for 15 min at 40-50 °C. The free base was extracted with tert-butyl methyl ether (3x200 mL), the organic phase was dried with anhydrous K2CO3, filtered, and concentrated on a water bath first at normal, then at reduced pressure. The residue was purified by recrystallization. |
Tags: 2094-74-8 synthesis path| 2094-74-8 SDS| 2094-74-8 COA| 2094-74-8 purity| 2094-74-8 application| 2094-74-8 NMR| 2094-74-8 COA| 2094-74-8 structure
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