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CAS No. : | 782-28-5 | MDL No. : | MFCD00114681 |
Formula : | C14H14O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HBRVUQIGDLSBCB-UHFFFAOYSA-N |
M.W : | 214.26 | Pubchem ID : | 220395 |
Synonyms : |
|
Num. heavy atoms : | 16 |
Num. arom. heavy atoms : | 10 |
Fraction Csp3 : | 0.21 |
Num. rotatable bonds : | 4 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 65.11 |
TPSA : | 37.3 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | Yes |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.98 cm/s |
Log Po/w (iLOGP) : | 2.07 |
Log Po/w (XLOGP3) : | 3.7 |
Log Po/w (WLOGP) : | 3.25 |
Log Po/w (MLOGP) : | 3.18 |
Log Po/w (SILICOS-IT) : | 3.41 |
Consensus Log Po/w : | 3.12 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.85 |
Log S (ESOL) : | -3.7 |
Solubility : | 0.043 mg/ml ; 0.0002 mol/l |
Class : | Soluble |
Log S (Ali) : | -4.17 |
Solubility : | 0.0144 mg/ml ; 0.000067 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -4.67 |
Solubility : | 0.0046 mg/ml ; 0.0000215 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 1.21 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P305+P351+P338-P280 | UN#: | N/A |
Hazard Statements: | H319-H317 | Packing Group: | N/A |
GHS Pictogram: |
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* 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 |
---|---|---|
47% | An addition funnel was installed on a tri-necked flask. Theflask was dried under vacuum, followed by being filled with nitrogen gas. The compound 14 (214 mg, 1 mmol) wasdissolved in benzene (5 mL, dehydrated and purified inadvance), followed by adding PC15 (270 mg, 1.3 mmol).After reacting at room temperature for 30 minutes, the flaskwas then placed in an ice bath. SnC14 (0.2 mL, 0.52 mg, 2 mmol) was added dropwisely through the addition funnelinto the flask at oo C. (about 20 minutes). After reacting for1 hour at oo C., the flask containing the reaction mixture wasput in the ice bath. The reaction mixture was extracted by EtOAc (30 mL) to collect the organic layer. The collectedorganic layer was dried by adding magnesium sulfate, andthen purified by colunm chromatography with a mixture ofEtOAc and hexanes (1/10) as an eluent to obtain compound15 (92 mg, yield: 47%). The above reaction is represented by the chemical equation (2-2).Spectral data as follow: M.W.: 196.24; 1H NMR (400MHz, CDC13 ) o9.40 (d, 1=8.7, lH), 7.92 (d, 1=8.3, lH), 7.80(d, 1=8.0, lH), 7.62 (t, 1=7.4, lH), 7.49 (t, 1=7.4, lH), 7.32 (d, 1=8.4, lH), 3.13 (t, 1=6.0, 2H), 2.79 (t, 1=6.5, 2H),2.23-2.17 (m, 2H); 13C NMR (100 MHz, CDC13 ) o200.46,198.55, 146.75, 142.94, 135.75, 134.22, 132.83, 131.42,130.05, 128.84, 128.80, 128.29, 127.34, 126.98, 126.95,126.71, 125.84, 124.84, 122.79, 41.12, 38.40, 31.63, 25.65,23.05, 22.79; TLC Rf=0.30 (EtOAc/hexanes, 1/10). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrahydrofuran; lithium aluminium tetrahydride; diethyl ether | ||
With lithium aluminium tetrahydride In diethyl ether | ||
0.92 g | With lithium aluminium tetrahydride In tetrahydrofuran for 2.5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With hydrazine In ethylene glycol Heating; | |
93% | With potassium hydroxide; hydrazine hydrate In diethylene glycol for 1.66667h; | |
91% | With hydrazine hydrate In diethylene glycol at 195℃; for 16h; |
86% | Stage #1: 4-(2-naphthyl)-4-oxobutyric acid With hydrazine hydrate In diethylene glycol at 100℃; for 1h; Inert atmosphere; Stage #2: With potassium hydroxide In diethylene glycol at 200℃; for 2h; Inert atmosphere; | 1 Synthesis of Compound 5: Under the protection of nitrogen, Compound 4 (2.6g, 10.9mmol, 1.0eq.), diethylene glycol (60mL) and hydrazine hydrate (2mL, 38.5mmol, 3.5eq.) were added to a 100mL flask, heated to 100 °C for 1h, and then added potassium hydroxide solids (1.46g, 36.3mmol, 3.3eq.), and then heated up to 200 °C for 2h. After cooling to room temperature, adding water (30mL) and 6mol/L hydrochloric acid (30mL) had a white precipitate precipitate, filtered to give Compound 5 (white solid powder, 2.1g), yield 86% |
85% | Stage #1: 4-(2-naphthyl)-4-oxobutyric acid With hydrazine hydrate In diethylene glycol at 100℃; for 1h; Inert atmosphere; Glovebox; Schlenk technique; Stage #2: With potassium hydroxide In diethylene glycol at 260℃; for 2h; Inert atmosphere; Glovebox; Schlenk technique; | |
76% | With potassium hydroxide; hydrazine hydrate In diethylene glycol at 200℃; for 6h; | |
73% | With 10 wt% Pd(OH)2 on carbon; hydrogen In acetic acid at 20℃; for 48h; | |
42% | With hydrazine hydrate; potassium hydroxide In diethylene glycol at 100 - 230℃; for 1.66667h; Inert atmosphere; | 8 Example 8: Synthesis of Compound 14( 4-(naphthalen-2-yl)butanoic acid) A two-necked flask was dried under vacuum, followed bybeing filled with nitrogen gas. The compound 13 (228 mg,1 mmol), hydrazine (0.05 mL, 1 mmol) and potassiumhydroxide (190 mg, 1.3 mmol) were dissolved in bis(2-hydroxy-ethyl) ether (1.7 mL), followed by heating to 100°C. for 100 minutes in an oil bath. Then, the flask wasremoved from the oil bath, followed by vacuum for 2-3hours. The flask was then filled with nitrogen gas and heatedto 230° C. for 5 hours. After the flask was cooled down, itwas then placed in an ice bath. The reaction mixture wasthen washed by hydrochloric acid (15 mL, 6N) for severaltimes to obtain a crude product. The crude product was then extracted by ether (100 mL) to collect the organic layer. Thecollected organic layer was dried by adding magnesiumsulfate, followed by condensation by a rotary evaporator.The resulting product was then recrystallized with cyclohexaneto obtain the compound 14 (90 mg, yield: 42%). The above reaction is represented by the chemical equation (2-1 ).Spectral data as follow: M.W.: 214.26; 1H NMR (400MHz, CDC13 ) o 7.79 (t, 1=8.5, 3H), 7.62 (s, lH), 7.45-7.41(m, 2H), 7.33 (d, 1=8.2, lH), 2.84 (t, 1=7.4, 2H), 2.41 (t,1=7.4, 2H), 2.06 (t, 1=7.4, 2H); 13C NMR (100 MHz CDC13 ) o 179.29, 138.69, 137.33, 133.63, 132.15, 128.82,128.07, 127.63, 127.47, 127.20, 126.94, 126.65, 126.23,125.99, 125.93, 125.54, 125.51, 125.28, 123.71, 35.16,33.57, 33.26, 32.21, 26.09, 25.51 |
With hydrogenchloride; amalgamated zinc; acetic acid weiteres Reagens: Toluol; | ||
With hydrogenchloride; amalgamated zinc | ||
With hydrazine hydrate; diethylene glycol | ||
With sodium hydroxide; hydrazine hydrate In diethylene glycol at 200 - 220℃; | ||
With hydrogenchloride; mercury; zinc Yield given; | ||
With potassium hydroxide; hydrazine hydrate In diethylene glycol | ||
With potassium hydroxide; hydrazine hydrate In ethylene glycol for 1.5h; Heating; | ||
94.9% by weight | With potassium hydroxide; hydrazine hydrate In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol | 1.ii Preparation of the compound having the formula STR3 (ii) To 300 ml of triethylene glycol contained in a 1-liter, 3-neck flask equipped with a magnetic stirrer, thermometer and take-off condenser was added 77.0 g (0.34 mole) of 4-(2-naphthyl)-4-oxobutyric acid, 61.2 g (1.09 moles) potassium hydroxide pellets and 45.44 ml of hydrazine monohydrate. The reaction mixture was heated up to 100°-110° C. with stirring and held there for 90 minutes. The temperature was gradually increased to 195° C. over 4 hours. Strong gas evolution commenced at about 130° C. with some distillate coming over above 140° C. The reaction mixture was allowed to cool and then stirred at room temperature overnight. Next morning the reaction mixture was diluted with ice water and while cooling in ice was acidified with conc. hydrochloric acid. The white solids were collected by filtration, washed with warm water and air-dried to yield 69.0 g (94.9% by weight yield) of γ-(2-naphthyl) butyric acid. M.P. 96°-99° C.; M/e 214; λmax 276 (5,580) ethanol. |
94.9% by weight | With potassium hydroxide; hydrazine hydrate In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol | 2.ii Preparation of the compound having the formula STR4 (ii) To 300 ml of triethylene glycol contained in a 1-liter, 3-neck flask equipped with a magnetic stirrer, thermometer and take-off condenser was added 77.0 g (0.34 mole) of 4-(2-naphthyl)-4-oxobutyric acid, 61.2 g (1.09 moles) potassium hydroxide pellets and 45.44 ml of hydrazine monohydrate. The reaction mixture was heated up to 100°-110° C. with stirring and held there for 90 minutes. The temperature was gradually increased to 195° C. over 4 hours. Strong gas evolution commenced at about 130° C with some distillate coming over above 140° C. The reaction mixture was allowed to cool and then stirred at room temperature overnight. Next morning the reaction mixture was diluted with ice water and while cooling in ice was acidified with conc. hydrochloric acid. The white solids were collected by filtration, washed with warm water and air-dried to yield 69.0 g (94.9% by weight yield) of γ-(2-naphthyl) butyric acid. M.P. 96°- 99° C.; M/e 214; λmax 276 (5,580) ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium on activated charcoal at 245 - 320℃; anschliessendes Behandeln mit aethanol. Alkalilauge; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride In benzene for 1h; Heating; | ||
With phosphorus pentachloride | ||
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With sulfuric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | In various solvent(s) at 210℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With phosphorus pentachloride; tin(IV) chloride 2.) benzene; Multistep reaction; | ||
Multi-step reaction with 2 steps 1: 1.) PCl5, 2.) SnCl4 / 2.) benzene 2: 8.3 percent / TiCl3, LiAlH4 / tetrahydrofuran / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With phosphorus pentachloride; tin(IV) chloride 2.) benzene; Multistep reaction; | ||
Multi-step reaction with 2 steps 1: 1.) PCl5, 2.) SnCl4 / 2.) benzene 2: 2.5 percent / TiCl3, LiAlH4 / tetrahydrofuran / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium on activated charcoal at 245 - 320℃; anschliessendes Behandeln mit aethanol. Alkalilauge; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 37 percent / AlCl3 / nitrobenzene / 16 h / 20 °C 2: 91 percent / H2NNH2*H2O / bis-(2-hydroxy-ethyl) ether / 16 h / 195 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 96 percent / CH3SO3H / 1 h / 90 °C 2: 86 percent / NaOMe / benzene / 12 h / 25 °C 3: 82 percent / triphenylmethanol; CF3COOH / 2 h / Heating 4: 90 percent / ethanol / 18 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 96 percent / CH3SO3H / 1 h / 90 °C 2: 86 percent / NaOMe / benzene / 12 h / 25 °C 3: 82 percent / triphenylmethanol; CF3COOH / 2 h / Heating 4: 91 percent / ethanol / 18 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 96 percent / CH3SO3H / 1 h / 90 °C 2: 86 percent / NaOMe / benzene / 12 h / 25 °C 3: 82 percent / triphenylmethanol; CF3COOH / 2 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 96 percent / CH3SO3H / 1 h / 90 °C 2: 86 percent / NaOMe / benzene / 12 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: AlCl3 / nitrobenzene / 12 h 2: N2H4*H2O, KOH / ethane-1,2-diol / 1.5 h / Heating | ||
Multi-step reaction with 2 steps 2: H2NNH2*H2O, KOH / bis-(2-hydroxy-ethyl) ether |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 60 percent / H2SO4 2: 50 percent / Pd/C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 60 percent / H2SO4 2: 50 percent / Pd/C 3: 23 percent / acetic acid, 70percent HNO3 / 3 h / 60 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 60 percent / H2SO4 2: 50 percent / Pd/C 3: 23 percent / acetic acid, 70percent HNO3 / 3 h / 60 °C 4: 87 percent / p-toluenesulfonyl chloride, N,N-diethylaniline / 8 h / 80 - 90 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 60 percent / H2SO4 2: 50 percent / Pd/C 3: 23 percent / acetic acid, 70percent HNO3 / 3 h / 60 °C 4: 87 percent / p-toluenesulfonyl chloride, N,N-diethylaniline / 8 h / 80 - 90 °C 5: 83 percent / methanol; dimethylsulfoxide / 2 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 74 percent / polyphosphoric acid / 6 h / 75 - 80 °C 2: Zn/Hg, I2 / benzene; diethyl ether / 3 h / Heating 3: HCOOH / 1 h / 70 °C 4: 23 percent / sulphur / 0.67 h / 270 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 74 percent / polyphosphoric acid / 6 h / 75 - 80 °C 2: Zn/Hg, I2 / benzene; diethyl ether / 3 h / Heating 3: 38 percent / formic acid / 1 h / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 74 percent / polyphosphoric acid / 6 h / 75 - 80 °C 2: Zn/Hg, I2 / benzene; diethyl ether / 3 h / Heating 3: 59 percent / formic acid / 1 h / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 74 percent / polyphosphoric acid / 6 h / 75 - 80 °C 2: Zn/Hg, I2 / benzene; diethyl ether / 3 h / Heating 3: 1.) formic acid, 2.) S / 1.) 70 deg C, 1 h, 2.) 270 deg C, 40 min 4: aq. 10percent NaOH / ethanol / 14 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 74 percent / polyphosphoric acid / 6 h / 75 - 80 °C 2: Zn/Hg, I2 / benzene; diethyl ether / 3 h / Heating 3: HCOOH / 1 h / 70 °C 4: sulphur / 0.67 h / 270 °C 5: aq. 20percent NaOH / ethanol / 16 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 74 percent / polyphosphoric acid / 6 h / 75 - 80 °C 2: Zn/Hg, I2 / benzene; diethyl ether / 3 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 74 percent / polyphosphoric acid / 6 h / 75 - 80 °C 2: Zn/Hg, I2 / benzene; diethyl ether / 3 h / Heating 3: 1.) formic acid, 2.) S / 1.) 70 deg C, 1 h, 2.) 270 deg C, 40 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 74 percent / polyphosphoric acid / 6 h / 75 - 80 °C 2: Zn/Hg, I2 / benzene; diethyl ether / 3 h / Heating 3: HCOOH / 1 h / 70 °C 4: sulphur / 0.67 h / 270 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 74 percent / polyphosphoric acid / 6 h / 75 - 80 °C 2: Zn/Hg, I2 / benzene; diethyl ether / 3 h / Heating 3: HCOOH / 1 h / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 10.9 g / aluminium trichloride / nitrobenzene / 12 h / 25 °C 2: 96 percent / hydrazine / ethane-1,2-diol / Heating | ||
Multi-step reaction with 2 steps 1: 36 percent / AlCl3 2: 93 percent / KOH, hydrazine hydrate / bis-(2-hydroxy-ethyl) ether / 1.67 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: LiAlH4 / diethyl ether 2: phosphorus tribromide / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: AlCl3 / benzene 2: N2H4*H2O, KOH / bis-(2-hydroxy-ethyl) ether / Heating 3: H2SO4 4: Pd-C / Heating 5: (saponification) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: N2H4*H2O, KOH / bis-(2-hydroxy-ethyl) ether / Heating 2: H2SO4 3: Pd-C / Heating 4: (saponification) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen In methanol for 12h; | 2; 3 Commercially available 2-naphthylacetic acid (3 g, 16.1 mmol) m 8 mL of anhydrous diethyl ether was added dropwise to a solution of lithium aluminum hydride (1.2 g, 32.2 mmol) in 8 mL of anhydrous diethyl ether under nitrogen atmosphere. The reaction mixture was aged for 2 h, quenched with aqueous Rochelle salt, stirred for an additional 2 h, partitioned between saturated aqueous NaHCO3 and diethyl ether, the organic phase was separated and dried over anhydrous sodium sulfate, and then evaporated under reduced pressure to provide the crude alcohol product (1.4 g). This alcohol (1.0 g, 5.81 mmol) was oxidized directly with iodobenzene diacetate (2.1 g, 6.5 mmol) and catalytic TEMPO (10%) in methylene chloride solvent (20 mL). The reaction mixture was quenched with aqueous sodium thiosulfate, partitioned with methylene chloride, the organic phase washed with aqueous NaHCO3, and the organic phase concentrated in vacuo to provide the clean aldehyde product. This crude aldehyde intermediate (500 mg, 2.9 mmol) was combined with methyl (triphenylphosphoranyhdene) acetate (1.47 g, 4.4 mmol) in toluene (10 mL), and the reaction mixture heated at reflux for 4 h. The mixture was concentrated in vacuo to a residue which was purified by flash column chromatography (S1O2, EtOAc/hexanes) to give the desired methyl enoate. This intermediate was then dissolved in tetrahydrofuran (10 mL), treated with aqueous 1N NaOH (5 mL), refluxed for 2 h, the mixture cooled, acidified and extracted with ethyl acetate. The organic phase was concentrated in vacuo to provide the enoic acid, which was treated with catalytic palladium on carbon in methanol (20 mL), and hydrogenated at 1 atmosphere with a hydrogen-filled balloon for 12 h. The reaction mixture was filtered over celite and concentrated in vacuo to provide the clean crude acid defined as Compound A in Scheme 2. Compound A (50 mg, 0.234 mmol) was converted into EXAMPLE 3 in a similar manner as m EXAMPLE 1 and illustrated in Scheme 1 using anthranihc acid directly in the amide coupling reaction The product Was purified via preparative RPHPLC and then recrystallization (diethyl ether/hexane) to give the desired product. 1H NMR (CDCl3, 500 MHz) δ 10.93 (s, 1H), 8 79 (d, 1H), 8.11 (d, 1H), 7.80(m, 3H), 7.68(s, 1H), 7.61(t, 1H), 7.40(m, 2H), 7.38 (d, 1H), 7.12 (t, 1H), 2.92 (t, 2H), 2.53 (t, 2H), 2.22 (m, 2H); LCMS m/z 332 (M+-1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With potassium hydroxide In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol at 140℃; | 4-(Naphthalen-2-yl)butanoic acid KOH (1.2 g, 21.0 mmol) was taken into triethylene glycol (10 mL) and heated to 100 °C until itdissolved to give a red/orange solution. 4-(2-(methoxycarbonyl)hydrazono)-4-(naphthalen-2-yl)butanoic acid ((1.3 g, 4.2 mmol) was added in one portion and the reaction heated at 140 °Covernight. The reaction was allowed to cool, diluted with water, acidified with 1 M HCl, and theaqueous phase extracted into EtOAc (3 x 20 mL). The organic phase was dried (MgSO4), filtered andthe solvent removed in vacuo. The crude product was purified by flash column chromatography(80% EtOAc/40-60 pet. ether) to give 4-(naphthalen-2-yl)butanoic acid as a tan solid (0.62 g, 2.9mmol, 69%).1H NMR (400 MHz, d6-DMSO): 12.08 (1H, s, OH), 7.88-7.81 (3H, m, CHAr), 7.68 ( 1 H, s, CHAr), 7.46(2H, app. quin. d, J = 6.8, 1.4 Hz, CHAr), 7.38 ( 1 H, dd, J = 8.4, 1.4 Hz, CHAr), 2.76 (2H, t, J = 7.4 Hz,CH2), 2.26 (2H, t, J = 7.4 Hz, CH2), 1.89 (2H, quin., J = 7.4 Hz, CH2).13C NMR (100 MHz, d6-DMSO): 174.1 (C=O), 139.1 (CAr), 133.1 (CAr), 131.5 (CAr), 127.7 (CArH), 127.4(CArH), 127.2 (CArH), 126.1 (CArH), 125.9 (CArH), 125.1 (CArH), 34.4 (CH2), 33.0 (CH2), 26.0 (CH2).νmax (neat) cm-1 2943, 1685, 1507, 1432m, 1406, 1339, 1271, 1199.HRMS (-ESI) m/z [(M-H)- found 213.0927 C14H13O2 requires 213.0921].m.p. (EtOAc) 98 °C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: aluminum (III) chloride / nitrobenzene / 20 °C / Inert atmosphere 2: 10 wt% Pd(OH)2 on carbon; hydrogen / acetic acid / 48 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / dichloromethane; nitromethane / 1.5 h / Cooling with ice; Inert atmosphere; Glovebox; Schlenk technique 2.1: hydrazine hydrate / diethylene glycol / 1 h / 100 °C / Inert atmosphere; Glovebox; Schlenk technique 2.2: 2 h / 260 °C / Inert atmosphere; Glovebox; Schlenk technique | ||
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / nitrobenzene / 20 °C / Inert atmosphere 2.1: hydrazine hydrate / diethylene glycol / 1 h / 100 °C / Inert atmosphere 2.2: 2 h / 200 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With formic acid; bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In tetrahydrofuran at 100℃; Inert atmosphere; Sealed tube; Overall yield = 67 %; Overall yield = 45.7 mg; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: potassium carbonate; palladium diacetate / toluene / 3 h / 90 °C / Inert atmosphere 2: formic acid; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)] / tetrahydrofuran / 100 °C / Inert atmosphere; Sealed tube |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With palladium on activated carbon; hydrogen In methanol at 20℃; for 1h; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 0 - 20 °C 2: hydroxylamine hydrochloride; potassium carbonate / ethyl acetate; water / 12 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 0 - 20 °C 2: hydroxylamine hydrochloride; potassium carbonate / ethyl acetate; water / 12 h / 0 - 20 °C 3: dichloromethane / 0.5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 0 - 20 °C 2: hydroxylamine hydrochloride; potassium carbonate / ethyl acetate; water / 12 h / 0 - 20 °C 3: dichloromethane / 0.5 h / 20 °C 4: sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C22H26ClIrN2O3 / dichloromethane / 12 h / 40 °C / Sealed tube |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With propan-1-ol; bis(1,5-cyclooctadiene)nickel (0); potassium <i>tert</i>-butylate; 4,4-dibenzyl-2-(pyridin-2-yl)-4,5-dihydrooxazole at 60℃; Sealed tube; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(1,5-cyclooctadiene)nickel (0); potassium <i>tert</i>-butylate; butan-1-ol at 40℃; Sealed tube; Overall yield = 99 percent; Overall yield = 21.2 mg; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 17h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 17h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 17h; |