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CAS No. : | 2556-73-2 | MDL No. : | MFCD00003263 |
Formula : | C7H13NO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZWXPDGCFMMFNRW-UHFFFAOYSA-N |
M.W : | 127.18 | Pubchem ID : | 17369 |
Synonyms : |
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.86 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 40.66 |
TPSA : | 20.31 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.96 cm/s |
Log Po/w (iLOGP) : | 1.82 |
Log Po/w (XLOGP3) : | 0.17 |
Log Po/w (WLOGP) : | 0.64 |
Log Po/w (MLOGP) : | 0.83 |
Log Po/w (SILICOS-IT) : | 1.35 |
Consensus Log Po/w : | 0.96 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.74 |
Solubility : | 23.4 mg/ml ; 0.184 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.15 |
Solubility : | 89.2 mg/ml ; 0.701 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.12 |
Solubility : | 9.67 mg/ml ; 0.076 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.1 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302+H312+H332-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With Dimethylphenylsilane; C22H34O2RuSi4 In neat (no solvent) at 25℃; for 7h; Schlenk technique; | |
81% | Stage #1: 1-methyl-2-azepanone With dodecacarbonyl-triangulo-triruthenium; 1,1,3,3-tetramethyldisilazane In toluene at 20 - 50℃; for 24.17h; Inert atmosphere; Stage #2: With hydrogenchloride In 1,4-dioxane; ethyl acetate; toluene at 20℃; for 0.5h; Stage #3: With sodium hydroxide In dichloromethane; water at 20℃; for 0.5h; | |
81% | With bis(2-chlorophenyl)borinic acid; phenylsilane In neat (no solvent) at 20℃; for 12h; Sealed tube; Inert atmosphere; |
75% | With phenylsilane; caesium carbonate at 25℃; for 48h; Schlenk technique; | |
70% | With hydrogen In 1,2-dimethoxyethane at 170℃; for 32h; | |
60% | Stage #1: 1-methyl-2-azepanone With dimethyl sulfate at 80℃; for 3h; Inert atmosphere; Stage #2: With 5%-palladium/activated carbon; hydrogen; sodium methylate In methanol at 25℃; | 9 General procedure: A carboxylic acid amide (10 mmol) is admixed with dimethyl sulphate (1 ml, 10 mmol) and stirred under argon for 3 hours at 80° C., and then the product is taken up in 5 ml of absolute methanol. An autoclave is charged with catalyst (1 mol %) and 5 ml of 2M sodium methylate solution in methanol, flushed with argon and filled with the reaction solution in methanol. 40 bar of hydrogen are then injected in, and the mixture is stirred at 25° C. and a constant pressure until hydrogen absorption is no longer evident (1-2 h). After filtration over Celite, the filtrate is dissolved in 10 ml of 2N hydrochloric acid and washed with diethyl ether, the aqueous phase is rendered basic with 12 ml of 2N NaOH solution and etherified out. The combined organic phases are dried over K2CO3 and admixed with 10 ml of 1M HCl solution in diethyl ether. The solid amine hydrochloride is filtered off, washed with diethyl ether and dried in vacuo. |
55% | Stage #1: 1-methyl-2-azepanone With dimethyl sulfate at 80℃; for 3h; Inert atmosphere; Stage #2: With 5%-palladium/activated carbon; hydrogen; sodium methylate In methanol at 20℃; for 0.2h; Autoclave; | |
With lithium aluminium tetrahydride; diethyl ether | ||
99.2 % Chromat. | With triethylsilane In toluene at 100℃; | |
95 %Chromat. | With Dimethylphenylsilane In toluene at 110℃; for 8h; Inert atmosphere; | |
72 %Chromat. | With (5-bromobenzo[b]thiophen-2-yl)boronic acid; phenylsilane In toluene at 110℃; for 36h; Inert atmosphere; Schlenk technique; chemoselective reaction; | |
87 %Chromat. | With 5 wt% Re/TiO2; hydrogen In octane at 200℃; for 24h; Autoclave; | |
70 %Chromat. | With triethyl borane; phenylsilane; sodium hydroxide In tetrahydrofuran; tert-butyl methyl ether at 20℃; Inert atmosphere; Schlenk technique; Sealed tube; chemoselective reaction; | |
70 %Chromat. | With triethyl borane; phenylsilane; sodium hydroxide In tetrahydrofuran; tert-butyl methyl ether at 20℃; for 48h; Inert atmosphere; Schlenk technique; Glovebox; Sealed tube; | |
89 %Spectr. | With bis(trimethylsilyl)amide yttrium(III); 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In toluene at 100℃; for 24h; Sealed tube; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With Lawessons reagent In benzene for 4h; Heating; | |
88% | With bis(1,5-cyclooctadiylboryl)sulfide In n-heptane for 2h; Heating; | |
With pyridine; benzenesulfonyl chloride Einleiten von Schwefelwasserstoff in die Reaktionsloesung.; |
With phosphorous (V) sulfide; xylene | ||
With carbon disulfide; phosphorous (V) sulfide at 245℃; | ||
With benzyltriethylammonium tetrathiomolybdate; trichlorophosphate 1.) CH2Cl2, 0 deg C, 30 min; 2.) -78 deg C, RT, 15 min; Yield given. Multistep reaction; | ||
With Lawessons reagent | ||
Multi-step reaction with 2 steps 1: POCl3 / CH2Cl2 / 0.5 h / -78 °C 2: hexamethyldisilathiane / CH2Cl2 / 6 h / Ambient temperature | ||
Multi-step reaction with 2 steps 1: CH2Cl2 / 12 h / Ambient temperature 2: 87 percent / NaSH / acetone / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With sulfuric acid | |
With sulfuric acid | ||
Stage #1: 1-methyl-2-azepanone With barium dihydroxide In water at 110℃; for 18h; Stage #2: With carbon dioxide In water at 0℃; for 0.333333h; | 36 Example 36: R (5S)-3-(5-{2-fluoro-4-[(5R)-2-oxo-5-(1H-1, 2, 3-TRIAZOL-1-VLMETHYL)-1, 3- OXAZOLIDIN-3-VLLPHENVLLPVRIDIN-2-VL)-4, 5-DIHVDROISOXAZOL-5-VLLMETHYL 6- F (METHOXYCARBONYL) (METHYL) AMINOLHEXANOATE N-methyl-caprolactam (15 g, 118 mmol) was combined with barium hydroxide (10.1 g, 72 mmol) and water (150 ml). The suspension was warmed to 110 oC for 18 hours then cooled over an ice bath. Gaseous carbon dioxide was bubbled through the solution for 20 minutes. The suspension was filtered through a celite pad and the filtrate was concentrated to dryness. The residue was triturated with acetonitrile, collected, rinsed with ether and dried in vacuo to yield 6- (METHYLAMINO) hexanoic acid as a white solid (10.7 g). 6- (Methylamino) hexanoic acid (5 g, 34.5 mmol), and potassium carbonate (18 g, 130 mmol) were suspended in water (50 ML) and dioxane (25 ml) then cooled to O oC. Methyl chloroformate (13 ml, 168 mmol) was added over 1 minute, then the mixture was stirred and allowed to warm slowly to room temperature for 16 hours. Conc. HCl (20 ml) was added then the mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, evaporated and dried in vacuo to give 6- [ (methoxycarbonyl) (methyl) amino] hexanoic acid as a thick clear oil (5. 7 G). |
8.8 g | With potassium hydroxide In ethanol for 96h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 26% 2: 63% | With tetraethylammonium perchlorate at 10 - 20℃; anodic oxidation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lithium diisopropyl amide In tetrahydrofuran at -20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With lithium diisopropyl amide In tetrahydrofuran at 5 - 10℃; for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With lithium diisopropyl amide In tetrahydrofuran at 5 - 10℃; for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In tetrahydrofuran at 20℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With phosgene In chloroform; toluene at 0℃; for 5h; | ||
With trichlorophosphate In dichloromethane at -78℃; for 0.5h; | ||
With trichlorophosphate In dichloromethane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium iodide In acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In chloroform 1.) -78 deg C, 2.) 25 deg C; | |
73% | In chloroform at 25℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium isopropylate In isopropyl alcohol; toluene at 60℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 3% 2: 47% | With methyltriisopropoxytitanium(IV) In tetrahydrofuran at 65℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With phosgene In chloroform Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With phosgene In chloroform Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With zirconium(IV) chloride In tetrahydrofuran; diethyl ether 1.) -10 deg C, 0.5 h, 2.) 0 deg C to r.t., 4 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With (diisopropylamino)magnesium In diethyl ether at 0℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | Stage #1: 1-methyl-2-azepanone With 2,2,6,6-tetramethyl-piperidine; n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.333333h; Stage #2: 2-Chloroanisole In tetrahydrofuran; hexane for 0.5h; | |
23% | With 2,2,6,6-tetramethyl-piperidine; n-butyllithium In tetrahydrofuran; hexane at 0℃; for 2.33333h; | 1 Embodiment 1: preparation of compoundI: The 250 ml flask is added in three 65 ml anhydrous THF, slowly dropping 11.8mL2, 2, 6, 6-tetramethyl piperidine, then adding 45 ml n-BuLi (1.6M-hexane solution), stirring, cooling to 0 °C. The 8.92gN-methyl caprolactam dissolved in 15 ml anhydrous THF, in addition to the above-mentioned reaction solution, for 0 °C stirring 10 min later, by adding 45 ml n-BuLi (1.6M-hexane solution), to continue stirring 10 min later, by adding 10g adjacent chloroanisoles. Reaction 90 min after, adding 50 ml ice water, to continue stirring 30 min. The organic phase is removed by reduced pressure distillation, add 100 ml ethyl acetate is dissolved, using 4NHCl and saturated salt water washing, the organic phase with anhydrous Na2SO4drying, concentrating by silica gel column chromatography for purification, was eventually 3.77g strawcoloured solid (yield 23.0%). |
With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane; water | 7 Hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one EXAMPLE 7 Hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one Diisopropylamine (152 g) in tetrahydrofuran (150 ml) was added over 30 minutes to 15% butyl lithium in hexane (641 g, 1.50 mole) under nitrogen at 20°-25° C. with cooling and the mixture stirred 30 minutes at room temperature. N-methylcaprolactam (63.6 g) in tetrahydrofuran (60 ml) was added over 5 minutes below 25° C. with cooling, the mixture was stirred for one hour at room temperature and then o-chloroanisole (71.3 g) was added over 20 minutes keeping the temperature below 30° C. The reaction mixture was stirred for two hours, water (2. l.) was added, the product was extracted into ethyl acetate (2*1 l.), the extracts were combined, washed with 2 N hydrochloric acid (1. l.) and water (500 ml) and evaporated under reduced pressure to give 27.1 g oil. The crude product was purified by column chromatography by eluding through a basic alumina column with toluene and concentrating the fractions to yield 8.7 g of title compound with melting point 74°-76° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 1-methyl-2-azepanone With trichlorophosphate In dichloromethane at -78 - 25℃; for 0.75h; Stage #2: With [tetrabutylammonium]2[WSe4] In dichloromethane at -78 - 25℃; for 0.5h; Further stages.; | |
65% | With selenium; dichloromethylsilane; triethylamine In toluene at 115℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 1-methyl-2-azepanone With sodium hydroxide for 8h; Heating; Stage #2: With hydrogenchloride Stage #3: 5-bromo-2-fluorobenzaldehyde With sodium carbonate In water; dimethyl sulfoxide Heating; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | With 2,6-dichloropyridine N-oxide In benzene at 40℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Stage #1: 1-(dimethoxymethyl)-1H-benzo[d]imidazol; 1-methyl-2-azepanone With lithium diisopropyl amide In n-heptane; toluene at -78℃; for 2h; Stage #2: With hydrogenchloride In n-heptane; toluene at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | Stage #1: 1-methyl-2-azepanone With trichlorophosphate In dichloromethane Stage #2: Thiosalicylic acid In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: Lawesson's reagent 2.1: t-BuOK 3.1: CuI; Et3N / (Ph3P)2PdCl2 / CH2Cl2 / 24 h / Heating 3.2: 52 percent / tetrahydrofuran / 12 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: Lawesson's reagent 2.1: t-BuOK 3.1: CuI; Et3N / (Ph3P)2PdCl2 / CH2Cl2 / 24 h / Heating 3.2: 52 percent / tetrahydrofuran / 12 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: Lawesson's reagent 2.1: t-BuOK 3.1: CuI; Et3N / (Ph3P)2PdCl2 / CH2Cl2 / 24 h / Heating 3.2: 43 percent / tetrahydrofuran / 12 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: n-BuLi; 2,2,6,6-tetramethylpiperidine / hexane; tetrahydrofuran / 0.33 h / 0 °C 1.2: 40 percent / hexane; tetrahydrofuran / 0.5 h 2.1: BBr3 / CH2Cl2 / 0 °C | ||
Multi-step reaction with 2 steps 1: 1.) butyl lithium, diisopropylamine / 1.) hexane/THF, 0 to -10 deg C, 10 min, 2.) THF, amb. temp., 1.5 h 2: 88 percent / bromine / CH2Cl2 / 1 h / 30 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: n-BuLi; 2,2,6,6-tetramethylpiperidine / hexane; tetrahydrofuran / 0.33 h / 0 °C 1.2: 40 percent / hexane; tetrahydrofuran / 0.5 h 2.1: n-BuLi; 2,2,6,6-tetramethylpiperidine / hexane; tetrahydrofuran / 1 h / 0 °C 2.2: 56 percent / hexane; tetrahydrofuran / 0 - 20 °C 3.1: BBr3 / CH2Cl2 / 0 °C | ||
Multi-step reaction with 3 steps 1: 1.) butyl lithium, diisopropylamine / 1.) hexane/THF, 0 to -10 deg C, 10 min, 2.) THF, amb. temp., 1.5 h 2: 88 percent / bromine / CH2Cl2 / 1 h / 30 °C 3: 1.) butyl lithium, diisopropylamine / 1.) hexane/THF, reflux, 3 h, 2.) reflux, 3 h | ||
Multi-step reaction with 3 steps 1.1: 2,2,6,6-tetramethyl-piperidine; n-butyllithium / tetrahydrofuran; hexane / 2.33 h / 0 °C 2.1: 2,2,6,6-tetramethyl-piperidine; n-butyllithium / tetrahydrofuran; hexane / 1.25 h / 0 °C 2.2: 15.5 h / 20 °C / Cooling with ice 3.1: boron tribromide / dichloromethane / 3.5 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: n-BuLi; 2,2,6,6-tetramethylpiperidine / hexane; tetrahydrofuran / 0.33 h / 0 °C 1.2: 40 percent / hexane; tetrahydrofuran / 0.5 h 2.1: n-BuLi; 2,2,6,6-tetramethylpiperidine / hexane; tetrahydrofuran / 1 h / 0 °C 2.2: 56 percent / hexane; tetrahydrofuran / 0 - 20 °C | ||
Multi-step reaction with 4 steps 1: 1.) butyl lithium, diisopropylamine / 1.) hexane/THF, 0 to -10 deg C, 10 min, 2.) THF, amb. temp., 1.5 h 2: 88 percent / bromine / CH2Cl2 / 1 h / 30 °C 3: 90 percent / aq. sodium hydroxide / Ambient temperature 4: 1.) sodium amide / 1.) toluene, reflux, 2 h, 2.) THF, 2 h | ||
Multi-step reaction with 2 steps 1: 1.) butyl lithium, 2,2,6,6-tetramethylpiperidine / 1.) hexane/THF, 0 deg C, 10 min, 2.) 30 min 2: 1.) sodium amide / 1.) toluene, reflux, 2 h, 2.) THF, 2 h |
Multi-step reaction with 2 steps 1.1: 2,2,6,6-tetramethyl-piperidine; n-butyllithium / tetrahydrofuran; hexane / 2.33 h / 0 °C 2.1: 2,2,6,6-tetramethyl-piperidine; n-butyllithium / tetrahydrofuran; hexane / 1.25 h / 0 °C 2.2: 15.5 h / 20 °C / Cooling with ice |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: Et3N / toluene / 2 h / Heating 2: 78 percent / i-PrONa / toluene; propan-2-ol / 2 h / 60 °C | ||
Multi-step reaction with 2 steps 2: benzene |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen In water at 250℃; for 4h; | 3 Example 3; This example illustrates that adipic acid may be successfully hydrogenated in the presence of water and methyl amine to produce N-methyl-caprolactam. Ruthenium (IS) acetylacetonate (0.46mmols, 0. 18g) and 1,1, 1 tris (diphenyl-phosphinomethyl) ethane (6. 1mmols, 0. 38g), water (40.14g) adipic acid (ex Aldrich, 137 mmols, 20.06g) and 40wt% methylamine solution (260mmols, 20.15g) were transferred into a 300ml Hastelloy Parr autoclave. This was sealed and purged with hydrogen before being pressurised to 600 psig with hydrogen and heated to 250°C. Once 250°C had been achieved, the reactor was topped up with hydrogen to 1000 psig and this pressure was maintained throughout the reaction via a regulator. At the end of the reaction, after 4hrs, the hydrogen supply was isolated and the reactor cooled. At room temperature the headspace gas was vented. The product was removed from the reactor and analysed. The water and organic analysis was determined using an HP gas chromatograph equipped with a micro TCD (area%) : ammonia (1. 110) water (65.107), methyl amine (0.903) hexahydroazepine (1. 191) N-methylhexahydroazepine (1. 701) N-methyl caprolactam (16.045) caprolactam (2. 706) N, N' dimethyladipamide (1.794) others (9.443). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With hydrogenchloride In water | 122.2 N-Hydroxy-N-(2-naphthylmethyl-methylamino)hexanamide (209) Step 2: 6-N-Methylamino hexanoic acid (207) A mixture of N-methyl P-caprolactam 206 (1.1 g, 8.6 mmol) and 8N HCl (8 mL) and H2O (4 mL) was refluxed for 18 hours. The resulting solution was cooled to room temperature, diluted with H2O (20 mL) and the mixture was evaporated to dryness. Additional H2O (10 mL) was added and again removed in vacuo. The crude residue was triturated with acetone (2*5 mL), removing acetone each time. The resulting solid was dried in vacuo to yield the desired product 207 (1.21 g, 96%). MS (ESI)=146 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In hydrogenchloride; methanol; diethyl ether; dichloromethane | 3 Synthesis of Acid 17 Synthesis of Acid 17 Acid 17 is prepared according to the scheme shown in FIG. 3A, and the following description, which refers to compounds by their identifying numbers as set forth in FIG. 3A. A solution of N-methyl caprolactam 12 (158 mmol) in conc. HCl (250 mL) is heated to reflux for 5 days. The reaction mixture is cooled to room temperature and concentrated to give a brown oil. The crude oil is dissolved in MeOH (300 mL) and HCl gas is bubbled through the solution for 4 min (the total HCl uptake is approx. 24 g). The mixture is allowed to stir at room temperature overnight then concentrated. 20% methylene chloride/diethyl ether (150 mL) is added and the solids are scraped from the walls of the flask with a spatula. The mixture is stirred for 30 min, then filtered, and the filter cake washed with 10% methylene chloride/diethyl ether (2*50 mL). Drying (high vac.) to constant weight yields methyl 6-methylaminohexanoate hydrochloride 13 as a white solid in high purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE III Example I was repeated, with the exception that lights and heavies were removed from the crude caprolactam by distillation over a short vigreux column prior to the crystallization. 45.7 grams of distilled caprolactam, containing 2121 ppm of N-methyl caprolactam, 85 ppm of methyl-valerolactam and 69 ppm of valeramide among other impurities, was crystallized. 23.8 grams of pure caprolactam crystals were obtained, containing 39 ppm of N-methyl caprolactam, 1 ppm of methyl valerolactam and 2 ppm of valeramide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; triethylamine | Preparation of 4-fluoro-α-fluorostyrene Preparation of 4-fluoro-α-fluorostyrene 22.01 g of 4-fluoroiodobenzene (100 mmol), 0.225 g of palladium(II) acetate (1 mmol) and 25.30 g of triethylamine (250 mmol) were weighed out successively into a 250 ml steel autoclave and dissolved in approx. 60 ml of N-methylcaprolactam. After the autoclave had been closed, it was degassed twice and 16.00 g of vinylidene fluoride (250 mmol) were condensed in. The autoclave was heated to 115° C. in an oil bath, with vigorous stirring, and this temperature was maintained for approx. 18 h. After cooling to room temperature, the reaction solution was added to 200 ml of 5% hydrochloric acid. Extraction was carried out with a diethyl ether/pentane mixture (1:1). The organic phase was dried over sodium sulfate, filtered and concentrated on a rotary evaporator. The main product was obtained by vacuum distillation as a clear colorless liquid boiling at 52° C./28 Torr. Yield: 4.57 g (33 mmol/33% of theory). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium methylate | 4 N-methylcaprolactam EXAMPLE 4 N-methylcaprolactam 5.4 g (0.1 mol) of sodium methylate and 18.5 g (0.1 mol) of N-trimethylsilylcaprolactam are introduced successively into 150 ml of 1,2-dimethoxyethane, and the mixture is stirred at room temperature for 30 minutes. Then 11 g (0.1 mol) of methyl methanesulfonate are added dropwise. After the reaction mixture has been stirred at 50° C. for a further one hour, it is cooled, the sodium mesylate is removed by filtration with suction, and the filtrate is evaporated. The oily residue is distilled in vacuo. Boiling point (6 mm) 100°-102° C.; yield 8.9 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium In tetrahydrofuran; hexane | 1 3-Ethylhexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one EXAMPLE 1 3-Ethylhexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one a solution of butyl lithium (0.05 mole) in hexane (31.25 ml) was treated with 2,2,6,6-tetramethylpiperidine (8.5 ml), followed by dry tetrahydrofuran ("THF"; 100 ml) under an inert atmosphere at 0° C. The mixture was treated with a solution of N-methylcaprolactam (6.25 ml, 50 mM) in THF (20 ml) and stirred for 30 minutes. A solution of butyl lithium (0.05 mole) in hexane (31.25 ml), was added and the mixture stirred for 15 minutes. A solution of o-chloroanisole (6.2 ml) in THF (20 ml) was added slowly, the mixture stirred for 1.5 hours and treated with ethyl iodide (5.15 ml). After one hour, the reaction was quenched with water (100 ml) and the solvents removed under reduced pressure. The residue was partitioned between 2 N HCl (200 ml) and toluene (250 ml). The organic layer was washed with brine, dried and the solvents removed under reduced pressure, to give 3-ethylhexahydro-3-(3 -methoxyphenyl)-1-methyl-2H-azepin-2-one (5.5 g) b.p. 140°/0.1 mm. Recrystallisation from diisopropyl ether gave pure title compound (5.0 g) m.p. 68°-69° C., identical with authentic material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium In tetrahydrofuran; hexane | 2 Hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one EXAMPLE 2 Hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one A solution of butyl lithium (0.05 mole) in hexane (34.4 ml), was treated with 2,2,6,6-tetramethylpiperidine (9.3 ml) followed by dry THF (100 ml) under an inert atmosphere at 0° C. The mixture was treated with N-methylcaprolactam (6.9 ml, 55 mM) and stirred for 30 minutes. A solution of butyl lithium (0.05 mole) in hexane (34.4 ml) was added, the reaction mixture stirred 15 minutes then treated with o-chloroanisole (3.1 ml). After 30 minutes a solution of butyl lithium (0.05 moles) in hexane (31.25 ml) was added, the mixture stirred for 15 minutes and treated with o-chloroanisole (3.1 ml). After a further 30 minutes, the reaction was quenched with water (100 ml) and the solvents removed under reduced pressure. The residue was partitioned between 5 N HCl (100 ml) and toluene (250 ml). The organic phase was washed with brine, dried and the solvents removed under reduced pressure. Distillation of the residue gave crude title compound (5.4 g) b.p. 150°/0.5 mm. Recrystallisation from diisopropyl ether gave pure material (4.2 g), m.p. 74°-75° C. identical with authentic material. | |
With hydrogenchloride; n-butyllithium In tetrahydrofuran; hexane; toluene | 3 Hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one EXAMPLE 3 Hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one A solution of butyl lithium (0.05 moles) in hexane (31.25 ml), was treated with 2,2,6,6-tetramethylpiperidine (8.5 ml), followed by THF (100 ml) under an inert atmosphere at 0° C. A solution of N-methylcaprolactam (6.25 ml, 50 mM) in THF (20 ml) was added, the mixture stirred for 30 minutes and treated with a solution of butyl lithium (0.05 mole) in hexane (31.25 ml). After 15 minutes, o-chloroanisole (6.2 ml) was added and the mixture stirred for fifteen hours at ambient temperature. The reaction was quenched with water (100 ml), the solvents removed in vacuo and the residue partitioned beteen 5 N HCl (100 ml) and toluene (250 ml). The organic phase was washed with brine, dried and the solvents removed under reduced pressure. Distillation of the residue gave crude title compound (40%) b.p. about 140°/0.05 mm. Recrystallisation from isopropyl ether gave pure material (31%), m.p. 74°-75° C., identical with authentic material. | |
With n-butyllithium In tetrahydrofuran; hexane | 4.A Step A Step A Preparation of 3-(3-methoxy-phenyl)-1-methyl-azepan-2-one To 1.6 M n-BuLi in hexane (31.3 mL, 50 mmol) at 0° C. was added a solution of 2,2,6,6-tetramethyl piperidine (8.43 mL, 50 mmol) in anh. THF (100 mL) over 5 min. N-methylcaprolactam (6.41 mL, 50 mmol) in anhydrous THF (20 mL) was added. After stirring the reaction mixture for 10 min, a further portion of 1.6M n-BuLi in hexane (31.3 mL, 50 mmol) was added, the mixture was stirred for 10 min, and 2-chloroanisole (6.34 mL, 50 mmol) was added. After stirring for 30 min under Ar, the reaction was quenched with H2O, stirred for 30 min, concentrated in vacuo, diluted with EtOAc and washed with 5N HCl (100 mL) and brine. The organic layer was dried (MgSO4), concentrated and purified using SiO2 chromatography (10% EtOAc/CH2Cl2) to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | In water | C.1 COMPARISON EXAMPLE 1 COMPARISON EXAMPLE 1 50 g of N-methylaminocaproic acid are heated to 250° C. in a 100 ml three-necked flask equipped with internal thermometer and descending condenser. 5.8 g of water distil off. The contents of the flask are then cooled and the N-methylcaprolactam formed is distilled off at about 0.3 bar. 33.7 g of distillate (77% yield) which is identified gas chromatographically and IR spectroscopically as N-methylcaprolactam and 9.7 g of undistillable residue are obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20 g (88.85%) | In toluene | 7 EXAMPLE 7 STR14 A suspension of 8.42 g of 57% sodium hydride-mineral oil suspension (4.8 g NaH, 0.2M) was washed with 2*400 ml portions of dry toluene and the toluene washings were decanted. 350 ml of dry toluene was added and the suspension was mechanically stirred while a solution of 20 g (0.177M) of azacycloheptan-2-one in 50 ml of dry toluene was added dropwise over 1 hour. After the addition was over, the mixture was refluxed for 1 hour and then cooled to room temperature. 22.0 g (0.2M) of methyl mesylate was added dropwise over 1 hour and the reaction mixture was then warmed to 50° for 1 hour. The mixture was cooled, filtered and the filter cake was resuspended in 100 ml of dry toluene and filtered. This combined to yield 20 g (88.85%) of 1-methylazacycloheptan-2-one; b.p. 85°-87°/0.1 mm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20 g (88.85%) | With CaH2; NaH In toluene | 1 Preparation of 1-methyl-azacycloheptan-2-one EXAMPLE 1 Preparation of 1-methyl-azacycloheptan-2-one A suspension of 8.42 g of 57% NaH-mineral oil (4.8 g, 0.2 mole of NaH) was washed with 2 * 400 ml portions of dry toluene (distilled from CaH2). After the washing was completed, 350 ml of dry toluene was added and the suspension mechanically stirred while a solution of 20 g (0.177 mole) of azacycloheptan-2-one in 50 ml of dry toluene was added dropwise over 1 hour. After the addition was completed, the mixture was refluxed with stirring for 1 hour, then cooled to 25° C and 22.0 g (0.2 mole) of methyl mesylate was added dropwise over 1 hour. After the addition was complete, the mixture was warmed with stirring to 50° for 1 hour. The mixture was cooled, filtered and the solid was resuspended in 100 ml toluene and filtered. The combined filtrates were concentrated and the residue was distilled at 85°-87°/0.1mm to yield 20 g (88.85%) of product. On 5% SE-30 column it showed one peak. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; ammonia; trifluoroborane diethyl ether In dichloromethane; acetone; benzene | Hexahydro-2-imino-1-methyl-1H-azepine cyclohexanesulfamate Hexahydro-2-imino-1-methyl-1H-azepine cyclohexanesulfamate Epichlorohydrin (12.5 g., 0.14 m) is added rapidly to a stirred solution of boron trifluoride etherate (25.7 g., 0.18 m) in anhydrous ether (90 ml). After the initial vigorous exotherm, the mixture is refluxed for 3 hr. The ether is removed with a filter stick and the solid residue is washed twice with anhydrous ether. Dry methylene chloride (60 ml) is added to the triethyloxonium fluoroborate and hexahydro-1-methyl-1H-azepin-2-one (17 g., 0.13 m) in methylene chloride (20 ml) is added. The resulting solution is stirred overnight (about 15 hours) at room temperature. More methylene chloride is added and ammonia is bubbled into the solution. The mixture becomes exothermic and after 1/2 hr. it cools. After 3 hr., the ammonia addition is stopped, more methylene chloride is added and the mixture stirred overnight at room temperature. The inorganic material is filtered off and the filtrate evaporated to give 26 g. or residual oil which is washed with benzene to remove starting lactam. The benzene is decanted and the residual oil dried under vacuum to give 22.5 g. of fluoroborate salt as a waxy solid. The fluoroborate salt is converted to the free base in benzene using 50% NaOH (7 ml). The benzene layer is decanted, filtered and dried (K2 CO3). Evaporation gives 11.5 g. of oil which is dissolved in acetone (20 ml) and treated with a solution of cyclohexanesulfamic acid (16.4 g) in warm acetone (150 ml). The resulting mixture is warmed briefly on a steam bath and then chilled and filtered to yield the product, hexahydro-2-imino-1-methyl-1H-azepine cyclohexanesulfamate, m.p. 142°-144° C. After recrystallization from ethanol-ether, the m.p. is 143°-145° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With magnesium; diisopropylamine In tetrahydrofuran; dichloromethane; ethyl acetate | 12 Hexahydro-1-methyl-3-(3-oxocyclohexen-1-yl)-2H-azepin-2-one EXAMPLE 12 Hexahydro-1-methyl-3-(3-oxocyclohexen-1-yl)-2H-azepin-2-one 2-Bromopropane (12.3 g) was added to suspension of magnesium (2.43 g) in ether (50 ml) at such a rate to maintain gentle reflux and the mixture was stirred 30 minutes after addition was complete. Diisopropylamine (14 ml) was then added dropwise and the mixture stirred until the Gilman test showed negative (about 1 hour). N-methylcaprolactam (12.7 g) was added dropwise (exothermic). After addition of the N-methylcaprolactam, stirring became difficult due to separation of a sticky solid, which however redissolved on addition of THF (50 ml). After the addition was complete the reaction mixture was stirred for 30 minutes then treated dropwise with 3-isopropoxy-2-cyclohexenone (16.4 g) (exothermic) and stirred overnight. The reaction mixture was poured onto 2 N aq HCl (250 ml) and stirred for 30 minutes. Dichloromethane (300 ml) was added and the layers separated. The aqueous layer was extracted with dichloromethane (2*300 ml) and the combined organic phases dried (MgSO4). Removal of the solvents under reduced pressure followed by recrystallisation of the residue from ethyl acetate gave the title compound (13.2 g) identical with the product of Example 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dimethyl amine In benzene | 1 2-dimethylamino-1-methyl-4,5,6,7-tetrahydro-3H-azepinium methylsulfate EXAMPLE 1 2-dimethylamino-1-methyl-4,5,6,7-tetrahydro-3H-azepinium methylsulfate Stir 190 g of N-methylcaprolactam and 189 g of dimethylsulfate for 3 hours at 80° C. Cool the resulting reaction mixture to ambient temperature before shaking it with diethyl ether and then freeing it from solvent residue in vacuo to obtain 346 grams (g) of 2-methoxy-1-methyl-4,5,6,7-tetrahydro-3H-azepinium methylsulfate as a light yellow oil. Add this oil, drop by drop, to a solution of 110 g of dimethylamine in 600 milliliters (ml) of benzene while stirring and boil the thus-prepared admixture under reflux for 90 minutes. Collect the heavy phase and extract it several times with diethyl ether. Concentrate the produced yellowish oil in vacuo to obtain 336 g (93% of theory) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With DEANB/5 mol% SpiroCAT formulation In tetrahydrofuran at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With triisopropoxytitanium(IV) chloride; methyllithium In tetrahydrofuran; diethyl ether at -78 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; toluene at -78℃; for 3h; Inert atmosphere; Stage #2: With boron trifluoride diethyl etherate In tetrahydrofuran; toluene for 0.166667h; Inert atmosphere; Stage #3: 1-methyl-2-azepanone With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether; toluene at 0℃; for 3h; Inert atmosphere; | |
72% | Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran at -78℃; for 3h; Inert atmosphere; Stage #2: With boron trifluoride diethyl etherate In tetrahydrofuran for 0.166667h; Inert atmosphere; Stage #3: 1-methyl-2-azepanone With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With catalyst:[Rh(OCH3)(C8H12)]2 and silicaphosphine In hexane diboron, amide, catalyst:(Rh(OCH3)(C8H12))2, silica-supported triarylphosphine, hexane, 40°C, 12 h; | |
86% | With methoxy(cyclooctadiene)rhodium(I) dimer In hexane at 40℃; for 12h; Inert atmosphere; regioselective reaction; | |
82% | With C25H36O2P2Ru In neat (no solvent) at 120℃; for 24h; Green chemistry; |
70% | With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; C12H21NSi In tetrahydrofuran at 80℃; for 24h; Glovebox; Inert atmosphere; Sealed tube; regioselective reaction; | 4.2.5. General borylation procedure In a nitrogen-filled glove box, [Ir(OMe)(cod)]2, the desiredligand, and B2pin2 were weighed into separate test tubes, and thestarting amide was weighed into a 5 mL conical vial equipped witha stir bar. To the test tube containing [Ir(OMe)(cod)]2 was added~0.2 mL THF. The resulting solution was then transferred into thetest tube containing B2pin2. The contents of the first test tube wererinsed three times (~0.2 mL/rinse) and added to the test tubecontaining B2pin2. The solution of [Ir(OMe)(cod)]2 and B2pin2 wasthen transferred into the test tube containing the ligand by a similarrinsing procedure described above. Finally, the resulting solutionwas added to the 5 mL conical vial followed by the rinsing procedure. The conical vial was then sealed and placed in analuminum block pre-heated to the desired temperature andallowed to stir for the desired time. The vial was then opened,solvent was removed via rotary evaporation, and a 1H NMR spectrumof the crude material was recorded. The crude reactionmixture was passed through deactivated silica (35% H2O w/w) witha gradient solvent system of 10%e15% MeOH in EtOAc. The productwas then collected and dried overnight under high vacuum prior tocollecting the reported analytical data |
56% | With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 8-(diisopropylsilyl)quinoline In 1,4-dioxane at 120℃; for 20h; Inert atmosphere; Sealed tube; | General Procedure A for Amide-Directed C-H Borylation General procedure: To a 25 mL PTFE-valved reaction tube, equipped with stir bar, containing [(COD)Ir(OMe)]2 (0.0083 g, 0.0013 mmol), 8-(diisopropylsilyl)quinolone (0.0063 g, 0.0025 mmol), bis(pinacolato)diboron (0.3810 g, 1.500 mmol), and the amide (1.00 mmol) was added dioxane (2.0 mL). The tube was sealed and heated to 120 °C. After 20 h, the reaction was exposed to air and concentrated in vacuo. The crude mixture was purified by flash chromatography on deactivated silica gel (35% H2O w/w) using an ethyl acetate/methanol solvent mixture. The collected product was concentrated in vacuo and was filtered through a cotton plug (to remove any silica gel solubilized by the high concentrations of methanol) to yield the final product. All isolated products had been reported previously and the spectral data was consistent with that reported. |
67 mg | With methoxy(cyclooctadiene)rhodium(I) dimer In hexane at 60℃; for 2h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With di-tert-butyl peroxide; iron(II) chloride In chlorobenzene at 120℃; for 3h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64 %Spectr. | With sodium 2-methyl-2-adamantoxide; dichlorobis(dicyclohexylphosphinomethylpyridine)-ruthenium (II); hydrogen; sodium hydride In toluene; mineral oil at 160℃; for 24h; Inert atmosphere; Autoclave; | Representative procedure for hydrogenation of amides with (RUPCY/base = 1/10):The reaction of N-benzylbenzamide (3a) (conditions A Table 1,entry 1): no preactivation of catalyst. General procedure: Under a continuous Ar flow, 2-methyl-2-adamantanol (16.6 mg, 0.1 mmol), NaH (60% oil dispersion, 4.0 mg, 0.1 mmol), anhydrous toluene (1.5 mL) and a magnetic stirring bar were placed in a dried Teflon tube (21 mL capacity). The Teflon tube was stoppered with a rubber septum, and the mixture was stirred at room temperature for 2 h under Ar. After removing the septum, under a continuous Ar flow, to the mixture was added RUPCY (7.50 mg, 0.01 mmol) and N-benzylbenzamide (105.6 mg, 0.5 mmol). The Teflon tube was quickly inserted into an autoclave and the inside of the autoclave was purged several times with hydrogen gas (>5 MPa). The autoclave was pressurized with an 8 MPa of hydrogen gas at 25°C, and heated at 160°C for 24 h under stirring (800 rpm). The autoclave was cooled to room temperature in an ice-water (0°C) bath,and the reaction mixture was quenched with NH4Cl (5.3 mg, 0.1 mmol). The organic phase was removed in vacuo (ca. 100 mmHg, 40 °C). The residue was diluted with CDCl3, and analyzed by 1H NMR. The yields of benzyl alcohol (92%) and benzylamine (92%) were calculated based on the integral ratio among the signals of these compounds with respect to an internal standard (1,1,2,2-tetrachloroethane). Afterward, the reaction mixture was purified by column chromatography on silica gel (silica gel (ca. 100 g) was pretreated with Et3N (small amount)-Et2O/hexane (vol%: 2/3), eluent; Et2O/hexane = 2/3, then EtOAc/Et3N = 100/1) to give N-benzylbenzamide (7.7 mg, 0.036 mmol, 7%), benzyl alcohol (47.4 mg, 0.438 mmol, 88%) and benzylamine (44.1 mg, 0.4187 mmol, 82%). |
57 %Spectr. | With sodium 2-methyl-2-adamantoxide; C24H38Cl2N2P2Ru; hydrogen In toluene at 120 - 160℃; for 20h; Autoclave; Sealed tube; | A6 1) Preactivation of Catalyst In an argon gas atmosphere, a stirrer, a ruthenium complex (Compound 2b; RUPIP2) (0.0067 mmol, 3.98 mg) and sodium-2-methyl-2-adamantoxide (0.067 mmol, 12.6 mg) were placed in a dried fluororesin tube (30 mL). Thereafter, the tube containing this compound was rapidly inserted into an autoclave, and toluene (2.0 mL) was added in an argon atmosphere. Subsequently, the autoclave was hermetically sealed while being grounded, and hydrogen gas was introduced into the autoclave from a hydrogen compressed gas cylinder connected via a stainless-steel pipe, thereby substituting the inside of the autoclave with hydrogen gas. More specifically, 1-MPa hydrogen gas pressure was applied inside the autoclave, and then the hydrogen gas pressure was removed through a leak valve. This operation (substitution and desubstitution) was repeated 10 times. Finally, the hydrogen gas inside the autoclave was set to 1 MPa, and a reaction was performed for 5 hours using a constant-temperature bath at 160° C. (2) Hydrogenation Reaction of Substrate (0285) After the reaction was completed, the autoclave was cooled to substantially room temperature by being immersed in an icy bath. Then, the leak valve of the autoclave was opened and the hydrogen gas inside the autoclave was released into the air. Subsequently, in an argon gas atmosphere, the reaction solution (1.5 mL) was obtained from the autoclave using a gas-tight syringe, and placed in another autoclave (a stirrer, and N-benzylbenzamide (0.5 mmol, 105.63 mg) were placed in a dried fluororesin tube (30 mL) in an argon gas atmosphere; thereafter, the tube containing this compound was rapidly inserted into an autoclave, and the inside of the autoclave was substituted with argon). Subsequently, the autoclave was hermetically sealed while being grounded, and hydrogen gas was introduced into the autoclave from a hydrogen compressed gas cylinder connected via a stainless-steel pipe, thereby substituting the inside of the autoclave with hydrogen gas. More specifically, 1-MPa hydrogen gas pressure was applied inside the autoclave, and then the hydrogen gas pressure was removed through a leak valve. This operation (substitution and desubstitution) was repeated 10 times. Finally, the hydrogen gas inside the autoclave was set to 1 MPa, and a reaction was performed for 24 hours using a constant-temperature bath at 110° C. For 1H NMR analysis, an internal standard substance (mesitylene) was added to the solution. Based on the hydrogen atom amount of the internal standard substance, the yield of the reaction product was calculated. The results of the analysis showed that the yields of benzyl alcohol and benzylamine were both 86% (corresponding to Entry 8 in Table 2 described later). A hydrogenation reaction was performed in the same manner as in Reaction Example A5, except that the conditions specified in Table 2 were used. Tables 2 and 3 show the results. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With copper(l) chloride In chlorobenzene at 130℃; for 12h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With hydrogenchloride In water for 48h; Reflux; | |
98.1% | With hydrogenchloride; water for 19.5h; Reflux; | IV.I.4.I I. Synthesis of 6-Methylaminohexanoic acid hydrochloride from N-Methylcaprolactam A solution on N-methylcaprolactam (1.12 g, 8.81 mmol) in 5.3 mL of concentrated aqueous HC1 and 6.7 mL water is refluxed for 19.5 hours. The reaction mixture is allowed to cool to room temperature, and 20 mL of water is added. It is then concentrated. 10 mL of water is added, and the mixture is again concentrated. The following is performed twice: 5 mL of acetone is then added and the mixture is concentrated. It is dried in vacuo to yield product (1.57 g, 98.1%, 8.64 mmol) as a cream-colored semi-solid. (45-149) MS m/z MH+ 146; HNMR (300MHZ, DMSO-d6) δ: 1.24-1.34 (2H, m), 1.44-1.62 (4H, m), 2.18-2.23 (2H, t), 2.77-2.86 (2H, m), 8.70 (2H, br), 12.05 (1H, s, br). (45-149-1 NMR) |
With hydrogenchloride In water at 110℃; for 16h; | S-30.1 Step-1: Preparation of 6-(methylamino)hexanoic acid hydrochloride To N-methylcaprolactam (5 g, 39.3 mmol) was added conc. HCl ( 25 mL)- H2O (36 mL) at RT and the mixture was refluxed at 110 °C for 16 h. The reaction was monitored by TLC. After 16 h, the mixture was concentrated under reduced pressure. To the residue obtained was added 10 mL of H2O and again concentrated. The crude obtained was triturated with acetone/n-pentane (1:5) twice to afford the title compound.1H NMR (400 MHz, DMSO-d6) d 12.05 (1H, s, br), 8.70 (2H, br), 3.6 (s, 3H), 2.18-2.23 (2H, m), 2.77-2.86 (2H, m), 1.44-1.62 (2H, m), 1.24-1.34 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 1-methyl-2-azepanone With lithium diisopropyl amide In tetrahydrofuran; hexane at -78 - 0℃; for 0.666667h; Inert atmosphere; Stage #2: iodomethane-d3 In tetrahydrofuran at -78 - 0℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | Stage #1: 1-methyl-2-azepanone; N,N-dimethyl-formamide With trichlorophosphate In benzene for 5.5h; Reflux; Stage #2: phenylhydrazine hydrochloride In ethanol for 2h; Reflux; | |
11% | Stage #1: 1-methyl-2-azepanone; N,N-dimethyl-formamide With trichlorophosphate In benzene for 5.5h; Reflux; Stage #2: phenylhydrazine hydrochloride In ethanol for 2h; Reflux; | Synthesis of Compounds 5a-h (General Method) General procedure: A solution of POCl3 (65 mmol) in anhydrous benzene (10 ml) was stirred and cooled on a water bath, while a solution of the lactam 1a (15 mmol) or freshly distilled lactam 1b-d (30 mmol) and anhydrous DMF (33 mmol) in anhydrous benzene (8 ml) was added dropwise over 10-15 min. The reaction mixture turned into a yellowish two-phase system, which was further stirred and refluxed for 5.5 h on a water bath in a flask equipped with a reflux condenser, while protecting from air moisture, and left overnight. The flask with the reaction mixture was transferred to a rotary evaporator, benzene and the excess of POCl3 were removed by distillation over 1 h at 80°. The residue was cooled and cautiously treated with cold water (15 ml) (lactams 1b-d) or treated with ice (lactam 1a), while avoiding overheating, stirred until dissolution and maintained for 1-1.5 h. The obtained solution was mixed together with a solution or suspension of the arylhydrazine hydrochloride 4-d (15 mmol for the lactam 1a or 30 mmol for the lactams 1b-d) in ethanol (50 ml), refluxed for 2 h in a flask with a reflux condenser, and cooled in a refrigerator. The precipitate of compounds 5a-g was filtered off, washed with 50% ethanol and water, air-dried, and recrystallized from ethanol. The product 5h was isolated by evaporation of the reaction mixture under vacuum, treating the residue with benzene and water, agitation of the two-phase system and separation of the benzene layer, washing with 10% HCl and water, drying over MgSO4, and evaporation of benzene. The residue was treated with ether (30 ml), the undissolved debenzylated by-product 5g was filtered off and washed with ether. The ether solution was evaporated, the residue was crystallized from a 1:1 mixture of hexane and cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | Stage #1: 1-methyl-2-azepanone; N,N-dimethyl-formamide With trichlorophosphate In benzene for 5.5h; Reflux; Stage #2: N-benzyl-N-phenylhydrazine hydrochloride In ethanol for 2h; Reflux; | |
43% | Stage #1: 1-methyl-2-azepanone; N,N-dimethyl-formamide With trichlorophosphate In benzene for 5.5h; Reflux; Stage #2: N-benzyl-N-phenylhydrazine hydrochloride In ethanol for 2h; Reflux; | Synthesis of Compounds 5a-h (General Method) General procedure: A solution of POCl3 (65 mmol) in anhydrous benzene (10 ml) was stirred and cooled on a water bath, while a solution of the lactam 1a (15 mmol) or freshly distilled lactam 1b-d (30 mmol) and anhydrous DMF (33 mmol) in anhydrous benzene (8 ml) was added dropwise over 10-15 min. The reaction mixture turned into a yellowish two-phase system, which was further stirred and refluxed for 5.5 h on a water bath in a flask equipped with a reflux condenser, while protecting from air moisture, and left overnight. The flask with the reaction mixture was transferred to a rotary evaporator, benzene and the excess of POCl3 were removed by distillation over 1 h at 80°. The residue was cooled and cautiously treated with cold water (15 ml) (lactams 1b-d) or treated with ice (lactam 1a), while avoiding overheating, stirred until dissolution and maintained for 1-1.5 h. The obtained solution was mixed together with a solution or suspension of the arylhydrazine hydrochloride 4-d (15 mmol for the lactam 1a or 30 mmol for the lactams 1b-d) in ethanol (50 ml), refluxed for 2 h in a flask with a reflux condenser, and cooled in a refrigerator. The precipitate of compounds 5a-g was filtered off, washed with 50% ethanol and water, air-dried, and recrystallized from ethanol. The product 5h was isolated by evaporation of the reaction mixture under vacuum, treating the residue with benzene and water, agitation of the two-phase system and separation of the benzene layer, washing with 10% HCl and water, drying over MgSO4, and evaporation of benzene. The residue was treated with ether (30 ml), the undissolved debenzylated by-product 5g was filtered off and washed with ether. The ether solution was evaporated, the residue was crystallized from a 1:1 mixture of hexane and cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trichlorophosphate In benzene for 5.5h; Reflux; | ||
With trichlorophosphate In benzene for 5.5h; Reflux; | Synthesis of Compounds 5a-h (General Method) General procedure: A solution of POCl3 (65 mmol) in anhydrous benzene (10 ml) was stirred and cooled on a water bath, while a solution of the lactam 1a (15 mmol) or freshly distilled lactam 1b-d (30 mmol) and anhydrous DMF (33 mmol) in anhydrous benzene (8 ml) was added dropwise over 10-15 min. The reaction mixture turned into a yellowish two-phase system, which was further stirred and refluxed for 5.5 h on a water bath in a flask equipped with a reflux condenser, while protecting from air moisture, and left overnight. The flask with the reaction mixture was transferred to a rotary evaporator, benzene and the excess of POCl3 were removed by distillation over 1 h at 80°. The residue was cooled and cautiously treated with cold water (15 ml) (lactams 1b-d) or treated with ice (lactam 1a), while avoiding overheating, stirred until dissolution and maintained for 1-1.5 h. The obtained solution was mixed together with a solution or suspension of the arylhydrazine hydrochloride 4-d (15 mmol for the lactam 1a or 30 mmol for the lactams 1b-d) in ethanol (50 ml), refluxed for 2 h in a flask with a reflux condenser, and cooled in a refrigerator. The precipitate of compounds 5a-g was filtered off, washed with 50% ethanol and water, air-dried, and recrystallized from ethanol. The product 5h was isolated by evaporation of the reaction mixture under vacuum, treating the residue with benzene and water, agitation of the two-phase system and separation of the benzene layer, washing with 10% HCl and water, drying over MgSO4, and evaporation of benzene. The residue was treated with ether (30 ml), the undissolved debenzylated by-product 5g was filtered off and washed with ether. The ether solution was evaporated, the residue was crystallized from a 1:1 mixture of hexane and cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; water for 0.75h; | 3 Preparation of N-methylcaprolactamium chloride Example 3 Preparation of N-methylcaprolactamium chloride In a 100 mL round bottom flask, a solution of hydrochloric acid (5.28 g, 0.047 mol) was added to caprolactam (6.02 g, 0.047 mmol). After stirring for 0.75 h, volatiles were removed. If two compounds result due to the presence of water, distillation may be used to separate the mixture. 1H NMR (500 MHz, d6-DMSO): 1.46-1.63 (m, 6H), 2.40 (t, 2H), 2.81 (s, 3H), 3.33 (t, 2H). 13C NMR (125 MHz, d6-DMSO): 23.23, 27.40, 29.43, 35.65, 36.1, 50.88, 175.79. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.6% | With nitric acid In water at 20℃; for 4h; | 4 Preparation of N-methylcaprolactamium nitrate Example 4 Preparation of N-methylcaprolactamium nitrate In a 100 mL round bottom flask, nitric acid (0.51 g, 8.1 mmol) was added to a stirring solution of N-methylcaprolactam (1.02 g, 8.0 mmol) in water (5 mL). After stirring for four hours at room temperature, volatiles were removed producing a yellow orange liquid. Yield: 1.44 g, 94.6%. 1H NMR (500 MHz, CDCl3): 1.70 (m, 6H), 2.65 (t, 2H), 3.09 (s, 3H), 3.48 (t 2H), 11.51 (br s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.4% | With sulfuric acid In toluene at 20℃; for 4h; | 1 Preparation of N-methylcaprolactamium hydrogensulfate Example 1 Preparation of N-methylcaprolactamium hydrogensulfate In a 100 mL round bottom flask, sulfuric acid (0.77 g, 7.9 mmol) was added to a stirring solution of N-methylcaprolactam (1.00 g, 7.9 mmol) in toluene (5 mL). After stirring for four hours at room temperature, volatiles were removed producing a light orange liquid. Yield: 1.75 g, 98.4%. 1H NMR (500 MHz, CDCl3): 1.70 (m, 6H), 2.63 (t, 2H), 3.03 (s, 3H), 3.41 (t, 2H), 7.79 (br). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.48 g | In water at 20℃; for 4h; | 2 Preparation of N-methylcaprolactamium p-toluenesulfonate Example 2 Preparation of N-methylcaprolactamium p-toluenesulfonate In a 100 mL round bottom flask, p-toluenesulfonic acid monohydrate (1.35 g, 7.9 mmol) was added to a stirring solution of N-methylcaprolactam (1.00 g, 7.9 mmol) in water (5 mL). After stirring for four hours at room temperature, volatiles were removed producing an orange liquid. Yield: 2.48 g. 1H NMR (500 MHz, CDCl3): 1.70 (m, 6H), 2.36 (s, 3H), 2.77 (t, 2H), 3.03 (s, 3H), 3.48 (t, 2H), 7.20 (d, 2H), 7.77 (d, 2H), 8.05 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: 1-methyl-2-azepanone With n-butyllithium; N-cyclohexyl-2,6-diisopropylaniline In tetrahydrofuran; hexane at -40℃; for 0.5h; Cooling with ice; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane for 0.5h; Cooling with ice; Inert atmosphere; Stage #3: With bis(η3-allyl-μ-chloropalladium(II)); Allyl acetate In tetrahydrofuran; hexane at 23℃; for 4h; Cooling with ice; Inert atmosphere; | |
53% | Stage #1: 1-methyl-2-azepanone With bis(2,2,6,6-tetramethyl-1-piperidyl)zinc In 1,4-dioxane; toluene at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With nickel(II) bromide dimethoxyethane; allyl diethyl phosphate In 1,4-dioxane; toluene at 80℃; for 0.25h; Inert atmosphere; | |
53% | With nickel(II) bromide dimethoxyethane; allyl diethyl phosphate; bis(2,2,6,6-tetramethyl-1-piperidyl)zinc In 1,4-dioxane at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With dipotassium peroxodisulfate; potassium iodide at 80℃; for 6h; Schlenk technique; | (16) N-(1H-1,2,3-benzotriazol-1-ylmethyl)-N-methylacetamide(3a); typical procedure General procedure: A 50 mL Schlenk tube equipped with a stirrer bar was charged with KI (16.6 mg, 0.1 mmol), benzotriazole (59.5 mg, 0.5 mmol), DMA (2 mL), and K2S2O8 (270 mg, 1 mmol) under air. The mixture was then stirred at 80 °C for 6 h (TLC monitoring), poured into H2O (20 mL), and extracted with EtOAc (3 ×). Then the organic phase was evaporated under vacuum, and the crude product was purified by column chromatography [silica gel, PE-EtOAc (10:1 to 2:1)] to give a colorless oil; yield: 98 mg (96%); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium hydroxide; methanesulfonic acid; hydrogen; tris(acetylacetonato)ruthenium(III); [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine] In 1,4-dioxane at 220℃; for 70h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran at 0 - 25℃; Inert atmosphere; | General procedure: The following procedure is a representative. An oven-dried 50-mL round bottom flask was equipped with a magnetic stir bar and cooled under an argon atmosphere. N,N-Diethylbenzamide (0.886 g, 5 mmol, 1 equiv) was added to the flask. The flask was fitted with a rubber septum and purged with argon and cooled to 0 C. Anhydrous THF (5 mL) was added to the flask via a syringe. Diisobutylaluminum borohydride (6.0 mL, 5.5 mmol, 1.1 equiv) was added dropwise over 15 min with stirring. Upon the completion of the addition of diisobutylaluminum borohydride, the ice-bath was removed and the reaction mixture was allowed to stir at 25 C for one hour. The reduction was complete after one hour as evidenced by the disappearance of the signal due to diisobutylaluminum borohydride (d 36.81 p, J = 85 Hz) and appearance of asignal due to amine-borane complex (d 7.0 q, J = 96 Hz) in the 11B NMR spectral analysis of an aliquot. The reaction mixture was then concentrated under reduced pressure using a rota-vap and the reaction flask was recappedwith a septum. Methanol (15 mL) was added slowly to the residue (Caution Hydrogen evolution) and the mixture was stirred for one hour at 25 C. The reaction mixture was concentrated under reduced pressure using a rota-vap togive a white solid. Methanol (15 mL) and then conc. HCl (1 mL) were added and the mixture was refluxed for 1 h, then filtered and concentrated. Pentane(10 mL) and deionized water (5 mL) were added to the filtrate. The layers wereseparated and to the aqueous layer was added sodium hydroxide (NaOHpellets) until the pH of the aqueous layer was 10. The aqueous layer was thenextracted with diethyl ether (3 10 mL). The combined organic layers weredried with anhydrous MgSO4, filtered, and concentrated in vacuo (25 C,1 Torr). The product was essentially pure amine as evidenced by 1H, 13C and 11BNMR spectroscopic analyses. This workup procedure allowed the isolation ofessentially pure amine products without the need for further purificationtechniques, such as column chromatography, distillation, or recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | Stage #1: 1-methyl-2-azepanone With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: Cyclopentyl bromide In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: vinyltriphenylsilane With 18-crown-6 ether; potassium hexamethylsilazane at 50℃; for 0.5h; Inert atmosphere; Stage #2: 1-methyl-2-azepanone at 50℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With tert-butyl peroxyacetate; [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; trifluoroacetic acid In acetone at 20℃; for 24h; Irradiation; Sealed tube; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium <i>tert</i>-butylate at 80℃; for 2h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With C15H25Cl2N3NiO3; potassium <i>tert</i>-butylate In octane at 110℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 53% 2: 14% | Stage #1: 1-methyl-2-azepanone With n-butyllithium; diisopropylamine In tetrahydrofuran at -78 - 0℃; for 1h; Inert atmosphere; Stage #2: 3α,5-cyclo-22-iodo-5α-23,24-bisnorcholan-6β-ol 6-methyl ether In tetrahydrofuran at -78℃; for 24h; Inert atmosphere; | (Step 1) General procedure: nBuLi (2.6 M,1.10 mmol) was added to a solution of iPr2NH (1.10 mmol) in THF at -78 °C. After stirring for 15 min at -78 °C and for 15 min at 0 °C, the reaction mixture was cooled to -78 °C. γ-, δ- and ε-lactam lactam (1.75 mmol) was added to the reaction mixture at -78 °C. After stirring for 1hr at -78 °C, iodide (0.438 mmol) was added to the reaction mixture, then stirred for 1d at -78 °C, the reaction was stopped by adding brine, and the mixture was extracted with EtOAc (x3). The combined organic extract was washed with brine, dried (Na2SO4), and concentrated in vacuo. The residue was purified by flash silica gel column chromatography to afford lactams (less polar product and more polar product). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With 2,2':6,2''-terpyridine; manganese; (1,2-dimethoxyethane)dichloronickel(II); lithium chloride In 1,3,5-trimethyl-benzene at 170℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | With 2,2':6,2''-terpyridine; manganese; (1,2-dimethoxyethane)dichloronickel(II); lithium chloride In 1,3,5-trimethyl-benzene at 170℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | With 2,2':6,2''-terpyridine; manganese; (1,2-dimethoxyethane)dichloronickel(II); lithium chloride In 1,3,5-trimethyl-benzene at 170℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With 2,2':6,2''-terpyridine; manganese; (1,2-dimethoxyethane)dichloronickel(II); lithium chloride In 1,3,5-trimethyl-benzene at 170℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With tetrabutylammonium tetrafluoroborate In acetonitrile at 20℃; for 4h; Electrochemical reaction; Inert atmosphere; Green chemistry; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-methyl-2-azepanone With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: 1-Iodooctane In tetrahydrofuran; hexane at -30℃; for 3h; | 2.2 Preparation Example 2.2 Preparation and structural confirmation of 1-methyl-3-octylazacycloheptan-2-one (compound 3) Take 0.5mol of diisopropylamine and 250mL of tetrahydrofuran, put them in a three-necked round bottom flask, cool to 0, add dropwise 2.5M n-butyllithium/n-hexane solution with 0.5mol n-butyllithium content under stirring .After stirring for 15 minutes at 0°C, the reaction solution was cooled to -78°C, and 0.5 mol of 1-methylazeppan-2-one was slowly added to it. After stirring at -78°C for 30 minutes, 0.55 was added all at once. mol n-octyl iodine.The mixture was stirred at -30°C for 3 hours and then warmed to room temperature.The lower layer reaction containing the target compound was collected by the slow decant method, and then water was added, and the resulting amide was extracted with chloroform.The organic phase is dried on magnesium sulfate, concentrated, and then distilled under atmospheric pressure. The fraction at 179-183°C is collected to obtain a colorless liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With palladium on activated charcoal; hydrogen at 100℃; for 18h; | 2 Example 2: Preparation of /V-methyl caprolactam Caprolactam (40.0 g, 0.353 mol) was added to a reaction vessel, followed by paraformaldehyde (42.5 g, 1.41 mol). A 10% palladium on carbon catalyst (4.05 g, 0.004 mol) was added. The reaction vessel was sealed, then purged and charged with Eh (150 psi). The mixture was heated to 100°C and stirred for 18 hours. GC analysis showed that N- methyl caprolactam was formed in 71% yield. After filtration, the filtrate was distilled to obtain the pure N-methyl caprolactam product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With lithium diisopropyl amide In tetrahydrofuran at 0 - 75℃; for 24h; | Compounds 5a-5n and 6a-6l; General Procedure General procedure: All reactions were carried out on 0.5-mmol scale. A reaction tube wascharged with amide (1.0 equiv), THF (3 mL) was added and the tubecooled to 0 °C. Then, LDA (1.5 equiv) was added and stirring continued for 15 min at 0 °C followed by addition of trialkyl phosphate (1.5equiv). Then, this reaction mixture was heated to the required temperaturefor 24 h. After that, the reaction was quenched with NH4Cland the mixture extracted with EtOAc. The organic layer was driedover Na2SO4 and concentrated to obtain crude product which was purifiedby column chromatography (EtOAc/hexane) to afford the desiredproduct 5 and 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With tert-butylethylene; C27H41NOP2Ru In neat (no solvent) at 150℃; for 18h; Schlenk technique; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(triphenylphosphine)carbonyliridium(I) chloride In tetrahydrofuran at 22℃; for 0.5h; Sealed tube; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: bis(triphenylphosphine)carbonyliridium(I) chloride / tetrahydrofuran / 0.5 h / 22 °C / Sealed tube; Inert atmosphere 2: tetrahydrofuran / 1 h / 22 °C / Inert atmosphere; Sealed tube |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With dipotassium peroxodisulfate In water at 20℃; for 24h; Irradiation; Schlenk technique; Green chemistry; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium tetrafluoroborate; (pentamethylcyclopentadienyl)titanium(IV) trichlorid; magnesium; dimethylsilicon dichloride In tetrahydrofuran at 60℃; for 16h; Inert atmosphere; Sealed tube; diastereoselective reaction; |
Tags: 2556-73-2 synthesis path| 2556-73-2 SDS| 2556-73-2 COA| 2556-73-2 purity| 2556-73-2 application| 2556-73-2 NMR| 2556-73-2 COA| 2556-73-2 structure
[ 1373223-45-0 ]
4-Amino-1-methylpiperidin-2-one hydrochloride
Similarity: 0.85
[ 7336-15-4 ]
3-(2-Oxoazepan-1-yl)propanenitrile
Similarity: 0.88
[ 6882-68-4 ]
(41S,7aR,13aR,13bR)-Dodecahydro-1H-dipyrido[2,1-f:3',2',1'-ij][1,6]naphthyridin-10(41H)-one
Similarity: 0.80
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