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CAS No. : | 3470-50-6 | MDL No. : | MFCD00156670 |
Formula : | C10H10O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | FNSQPQKPPGALFA-UHFFFAOYSA-N |
M.W : | 162.19 | Pubchem ID : | 4679494 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.3 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 46.32 |
TPSA : | 37.3 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) : | -6.1 cm/s |
Log Po/w (iLOGP) : | 1.55 |
Log Po/w (XLOGP3) : | 1.67 |
Log Po/w (WLOGP) : | 1.91 |
Log Po/w (MLOGP) : | 1.35 |
Log Po/w (SILICOS-IT) : | 2.52 |
Consensus Log Po/w : | 1.8 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.27 |
Solubility : | 0.876 mg/ml ; 0.0054 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.07 |
Solubility : | 1.39 mg/ml ; 0.00856 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.81 |
Solubility : | 0.252 mg/ml ; 0.00155 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.58 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | 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 |
---|---|---|
97% | With potassium carbonate In acetone for 6 h; Reflux | General procedure: 6-Hydroxy-1-tetralone (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
97% | With potassium carbonate In acetone for 6 h; Reflux | General procedure: 6-Hydroxy-1-tetralone (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. 6-(Benzyloxy)-3,4-dihydronaphthalen-1(2H)-one (6a) The title compound was prepared in a yield of 97percent: mp 100.9–102.1 °C (cyclohexane). 1H NMR (BrukerAvance III 600, CDCl3) δ 2.09 (p, J = 6.5 Hz, 2H), 2.56 – 2.61 (m, 2H), 2.90 (t, J = 6.1 Hz, 2H), 5.09 (s,2H), 6.77 (d, J = 2.2 Hz, 1H), 6.88 (dd, J = 8.7, 2.6 Hz, 1H), 7.30 – 7.36 (m, 1H), 7.36 – 7.43 (m, 4H),8.00 (d, J = 8.7 Hz, 1H); 13C NMR (Bruker Avance III 600, CDCl3) δ 23.29, 30.10, 38.85, 69.20, 113.53,113.58, 122.11, 126.64, 128.99, 129.67, 131.78, 135.20, 146.94, 162.30, 197.08; APCI-HRMS m/z: calcdfor C17H17O2 (MH+), 253.1223, found 253.1220. |
94% | With potassium carbonate In acetonitrile at 50℃; for 2 h; | Step 1: Preparation of 6-benzyloxytetralin-1-one To a solution of 6-hydroxytetralin-l-one (100 g, 616.56 mmol, 1.00 eq) in acetonitrile (1000 mL) was added potassium carbonate (170.43 g, 1.23 mol, 2.00 eq) and benzyl bromide (126.54 g, 739.87 mmol, 88 mL, 1.20 eq). The reaction mixture was stirred at 50° C. for 2 hours. TLC (petroleum ether:ethyl acetate=5:1) showed most of the starting material was consumed. Water (1000 mL) was added to the mixture, the resulting mixture was extracted with ethyl acetate (600 mL*3). The combined organic phase was washed with brine (800 mL), dried over sodium sulfate, filtered and concentrated in vacuum. The residue was triturated with petroleum ether and ethyl acetate (303 mL, petroleum ether:ethyl acetate=100:1, V:V). The mixture was filtered and the filter cake was washed with petroleum ether (50 mL*2), dried in vacuum to give 6-benzyloxytetralin-1-one (146 g, 578.65 mmol, 94percent yield) as a brown solid. 1H-NMR (400 MHz, CDCl3) δ 8.02 (d, J=8.8 Hz, 1H), 7.45-7.34 (m, 5H), 6.91 (dd, J=8.8, 2.4 Hz, 1H), 6.80 (d, J=2.4 Hz, 1H), 5.12 (s, 2H), 2.93 (t, J=6.0 Hz, 2H), 2.62 (t, J=6.4 Hz, 2H), 2.15-2.09 (m, 2H). |
84% | With potassium carbonate In acetonitrile at 15℃; for 3 h; | Step 1: 6-(Benzyloxy)-3,4-dihydronaphthalen-1(2H)-one 129a To a mixture of 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one 101f (20.0 g, 123.31 mmol) and benzyl bromide (20 mL, 246.62 mmol) in MeCN (70 mL) was added K2CO3 (33.2 g, 240.21 mmol) at 15° C. and the resulting mixture was stirred for 3 hours. The mixture was filtered, concentrated and the residue was purified by flash column chromatography eluted with 0-10percent EtOAc in petroleum ether to afford 129a (26 g, 84percent yield) as brown oil. 1H NMR (400 MHz, CDCl3) δ 8.06-7.98 (m, 1H), 7.46-7.32 (m, 5H), 6.90 (d, J=8.8 Hz, 1H), 6.80 (s, 1H), 5.16-5.08 (m, 2H), 2.93 (t, J=6.0 Hz, 2H), 2.62 (t, J=6.4 Hz, 2H), 2.17-2.06 (m, 2H). |
80% | With potassium carbonate In acetoneInert atmosphere of nitrogen; Heating; Reflux | The mixture of 6-hydroxy-3,4-dihydro-2H-naphthalen-l-one (30.74 g, 0.1895 mol), benzyl bromide (27.0 mL, 0.227 mol) and potassium carbonate (39.3 g, 0.284 mol) in acetone (250 mL, 3.4 mol) was heated to reflux under an atmosphere of nitrogen for 3 hours. The mixture was cooled to 10 °C with an ice bath, filtered and washed with small amount of acetone. The filtrate was concentrated in rotavap. The resulting crystals were collected by filtration and washed with EtOAc-hexane then hexane to give a pale yellow solid product as the first crop. The mother liquid was concentrated in rotavapor and the residue was purified by chromatograph with EtOAc:hexane (0:100 to 20:80) to give the second crop of solid product (38.07g, 80percent). 1H NMR (CHLOROFORM-d) δ: 8.02 (d, J = 8.6 Hz, IH), 7.32 - 7.51 (m, 5H), 6.91 (dd, J = 8.8, 2.3 Hz, IH), 6.80 (s, IH), 5.13 (s, 2H), 2.93 (t, J = 6.1 Hz, 2H), 2.56 - 2.68 (m, 2H), 2.12 (quin, J = 6.3 Hz5 2H). MS (M+l): 253.0. |
34.5g | With potassium carbonate In acetone at 40℃; for 3.5 h; | To a solution of 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one (CAS registry number: 3470-50-6) (24.3 g) inacetone (160 mL), benzyl bromide (29.4 mL) and potassium carbonate (31.1 g) were added at room temperature andthe mixture was stirred at 40°C for 3.5 hours. After insoluble matters were filtered off, the mixture was concentrated andwashed with a mixed solvent of tert-butyl methyl ether (MTBE)-hexane (1 : 4) to give the title compound (34.5 g) havingthe following physical property.TLC: Rf 0.38 (hexane : ethyl acetate = 3 : 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridine; at 20℃; | Step 1: 5-Oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate To a solution of 6-hydroxy-3,4-dihydro-2H-naphthalen-1-one (6.3 g, 39.1 mmol) in dry pyridine (30 mL) at 0 C. was added trifluoromethanesulfonic anhydride (7.3 mL, 43.0 mmol) over a few minutes. The solution was warmed to room temperature and stirred for 3 h. The reaction was poured into 1N HCl and diluted with ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate (11.5 g, 100%). The crude product was used without purification. MS(ES) m/z 295 [M+H]+. |
98% | With pyridine; In dichloromethane; at 0℃; for 0.5h;Inert atmosphere; | 2 g of 6-hydroxytetralone (12.3 mmol, 1 eq) is suspended under N2 in 90 ml of dichloromethane and cooled to 0 C. To the reaction mixture, dry pyridine (1.4 ml, 17.26 mmol, 1.4 eq) is added, followed by trifluoromethanesulfonic anhydride (2.33 ml, 4.17 g, 14.79 mmol, 1.2 eq). After 30 min at 0 C., the reaction is stopped by adding a saturated sodium carbonate solution, and washed with water. The organic phase is dried over MgSO4, filtered, and the solvent is removed in vacuum on a rotary evaporator. The brown oil obtained was used for further synthesis without further purification (3.7 g, 98% yield). C11H9F3O4S; MW 294; 1H-NMR (CDCl3): δ 8.12 (d, J=8.5 Hz, 1H), 7.20-7.17 (d, J=12.0 Hz, 2H); 3.01 (t, J=6.0 Hz, 2H); 2.67 (t, J=6.3 Hz, 2H); 2.19-2.14 (q, J=7.3 Hz, 2H); 13C-NMR (CDCl3): δ 196.4, 152.4, 147.1, 132.40, 130.0, 121.4, 119.7, 38.8, 29.7, 22.9; IR: 2937, 2851, 1692, 1605, 1425, 1219, 897 1/cm |
95.2% | With triethylamine; In dichloromethane; at 20℃; for 2h; | A solution of 6-hydroxy-1-naphtholone (8.1 g, 50 mmol/L)was dissolved in dichloromethane (50 mL), and then 20 mLdichloromethane solution of Tf2O (14.1 g) was slowlydropwised into the mixture, followed by 20 mL dichloromethanecontaining tris ethylamine (5.05 g) was dropwised.The reaction mixture was allowed to stand at roomtemperature for 2 h. Next, the reaction solution was washedtwo times with dilute NaHCO3 solution and two times withbrine. The organic phase was dried over anhydrous sodiumsulfate, filtered, and concentrated. |
94% | With pyridine; In dichloromethane; at 0 - 20℃; | Step 1 :Neat Tf2O (0.83 ml_, 4.9 mmol) is added dropwise to a cooled (00C) solution of phenol 18a (0.50 g, 3.1 mmol) and pyridine (1.3 ml_, 17 mmol) in DCM (15 ml_). The reaction is allowed to warm to RT and stir overnight. The reaction is quenched by the addition of a 10% citric acid solution (50 ml.) and the mixture is extracted with DCM (3 x 50 ml_). The combined organics are washed with water (50 ml_), dried over MgSO4, filtered and concentrated. The product is purified by CombiFlash Companion to give triflate 18b (500 mg, 94% yield). |
94% | With pyridine; In dichloromethane; at 0 - 20℃; | Neat Tf2O (0.83 ml_, 4.9 mmol) is added dropwise to a cooled (00C) solution of phenol 18a (0.50 g, 3.1 mmol) and pyridine (1.3 ml_, 17 mmol) in DCM (15 ml_). The reaction is allowed to warm to RT and stir overnight. The reaction is quenched by the addition of a 10% citric acid solution (50 mL) and the mixture is extracted with DCM (3 x 50 ml_). The combined organics are washed with water (50 mL), dried over MgSO4, filtered and concentrated. The product is purified by CombiFlash Companion to give triflate 18b (500 mg, 94% yield). |
94% | With pyridine; In dichloromethane; at 0 - 25℃; | Neat Tf2O (0 83 mL, 4 9 mmol) is added dropwise to a cooled (00C) solution of phenol 18a (0 50 g, 3 1 mmol) and pyridine (1 3 mL, 17 mmol) in DCM (15 mL) The reaction is allowed to warm to RT and stir overnight The reaction is quenched by the addition of a 10% citric acid solution (50 mL) and the mixture is extracted with DCM (3 x 50 mL) The combined organics are washed with water (50 mL), dried over MgSO4, filtered and concentrated The product is purified by CombiFlash Companion to give triflate 18b (500 mg 94% yield) |
94% | With pyridine; at 0 - 20℃; for 4h; | INTERMEDIATE 16-Vinyl-3, -dihydronaphthalen-l(2H)-one oximeStep A: 5-Oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate (I-IA)[00186] To a solution of 6-hydroxy-3,4-dihydronaphthalen-l(2H)-one (2 g, 12.33 mmol) in anhydrous pyridine (10 mL) was added trifluoromethanesulfonic anhydride (2.5 mL, 14.80 mmol) at 0 C over a period of 5 min. The reaction mixture was allowed to come to room temperature and stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure. The resulting brownish red residue was partitioned between ether (60 mL) and water (30 mL). The ether layer was sequentially washed with IN hydrochloric acid (20 mL), sat. aq. NaHC03 (20 mL), brine (20 mL), dried over sodium sulfate, concentrated, and purified by silica gel columnchromatography using hexane/ethyl acetate to yield 5-oxo-5,6,7,8-tetrahydronaphthalen- 2-yl trifluoromethanesulfonate (3.4 g, 11.55 mmol, 94 % yield) as a liquid. lH NMR (400 MHz, CDC13) δ ppm 8.14 (1 H, d, J=8.4 Hz), 7.17-7.24 (2 H, m), 3.02 (2 H, t, J=6.1 Hz), 2.69 (2 H, t, J=6.5 Hz), 2.15-2.22 (2 H, m). |
94.4% | With pyridine; In dichloromethane; at 0 - 20℃; for 8h; | To a solution of compound 1-1A (5.0 g, 30.83 mmol) and pyridine (3.0 g, 37.0 mmol) in DCM (60 mL) was added trifluoromethanesulfonic anhydride (10.44 g, 37.0 mmol) dropwise at 0 . After the addition, the mixture was stirred at rt for 8 hours, and then washed with water (30 mL). The organic layer was dried over anhydrous Na2SO4and concentrated in vacuo. The residue was purified by silica gel column chromatography (PE : EtOAc (V : V) 10 : 1) to give the title compound (8.5 g, 94.4) . 1H NMR (400 MHz, DMSO-d6) : δ 8.02 (d, J 8.7 Hz, 1H) , 7.54 (d, J 2.2 Hz, 1H) , 7.44 (dd, J 8.7, 2.4 Hz, 1H) , 3.02 (t, J 6.0 Hz, 2H) , 2.66-2.61 (m, 2H) , 2.10-2.03 (m, 2H) ppm. |
94% | With pyridine; In dichloromethane; at 0 - 20℃; | Neat Tf2O (0.83 ml_, 4.9 mmol) is added dropwise to a cooled (00C) solution of phenol 18a (0.50 g, 3.1 mmol) and pyridine (1.3 ml_, 17 mmol) in DCM (15 ml_). The reaction is allowed to warm to RT and stir overnight. The reaction is quenched by the addition of a 10% citric acid solution (50 mL) and the mixture is extracted with DCM (3 x 50 mL). The combined organics are washed with water (50 mL), dried over MgSO4, filtered and concentrated. The product is purified by CombiFlash Companion to give triflate 18b (500 mg, 94% yield). |
93% | With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 2h; | Example 1; Trifluoromethanesulfonic acid 5-oxo-5,6,7,8-tetrahvdro-naphthalen-2-yl ester; [00157] Trifluoromethanesulfonic anhydride (1.7 mL, 10 mmol) was added slowly over 1 hour to a solution of 6-hydroxy-l-tetralone (1.62 g, 10 mmol) and 2,6-lutidine (1.28 mL, 10 mmol) in dry dichloromethane (10 mL) cooled to 0 C. After 1 hour the solution was diluted with dichloromethane (10 mL) and washed with 1 M hydrochloric acid (20 mL). The organic layer was re-extracted with dichloromethane (50 mL) and the combined organics washed with 1 M hydrochloric acid (10 mL). The organics were dried over magnesium sulfate and concentrated under vacuum. The residue was purified by column chromatography (Silica gel, CH2CI2) to provide 2.7 g of compound 2 (93%).[00158] 1H NMR (300MHz, CDCl3) δ 2.13 (p, 2H, J= 6.22Hz), 2.63 (t, 2H, J = 6.95Hz), 2.98 (t, 2H, J = 6.22Hz), 7.15 (m, 2H), 8.07 (m, IH); 13C NMR δ 23.08, 29.88, 38.92, 116.74, 119.81, 121.56, 130.14, 132.58, 147.38, 152.52, 196.53. |
93% | With 2,6-dimethylpyridine; In dichloromethane; at 0 - 20℃; for 1 - 72h;Product distribution / selectivity; | Trifluoromethanesulfonic anhydride (1.7 niL, 10 mmol) was added slowly over 1 hour to a solution of 6-hydroxy-l-tetralone (1.62 g, 10 mmol) and 2,6-lutidine (1.28 mL, 10 mmol) in dry dichloromethane (10 mL) cooled to 0 C. After 1 hour the solution was diluted with dichloromethane (10 mL) and washed with 1 M hydrochloric acid (20 mL). The aqueous layer was re-extracted with dichloromethane (50 mL) and the combined organics washed with 1 M hydrochloric acid (10 mL). The organics were dried over magnesium sulfate and concentrated under vacuum. The residue was purified by column chromatography (Silica gel, CH2Cl2) to provide 2.7 g of compound 2 (93%).[00177] 1R NMR (300MHz, CDCl3) δ 2.13 (p, 2H, J= 6.22Hz), 2.63 (t, 2H, J = 6.95Hz), 2.98 (t, 2H, J = 6.22Hz), 7.15 (m, 2H), 8.07 (m, IH); 13C NMR δ 23.08, 29.88, 38.92, 116.74, 119.81, 121.56, 130.14, 132.58, 147.38, 152.52, 196.53.; Example 15: Trifluoro-methanesulfonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2- yl ester[00198] Trifluoromethanesulfonic anhydride (28 mL, 0.17 mol, Aldrich) was slowly added to a solution containing 6-hydroxy-3,4-dihydro-2H-naphthalen-l-one (25.45 g, 0.1569 mol, Aldrich) and 2,6-Lutidine (19 mL, 0.16 mol, Aldrich) in Methylene chloride (200 mL, Acros) at 0 C. Additional 2,6-Lutidine (2 mL, 0.02 mol, Aldrich) was then added and the reaction was stirred at room temperature for three days. The reaction was diluted with methylene chloride and washed once with IN HCl. The organic layer was then dried with magnesium sulfate and concentrated. The crude material was used without further purification in Example 16. MS: m/z=295.24 M+H. |
85% | With 2,6-dimethylpyridine; dmap; In dichloromethane; at 20℃; for 1h; | 10642] Triflic anhydride (16.7 g, 59.2 mmol) was added to an ice cold solution of product of Example 182A(8.0 g, 49.3 mmol), DMAP (1.20 g, 9.83 mmol) and 2,6-lutidine (5.20 g, 49.3 mmol) in dichloromethane (15 mE). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was then diluted with dichloromethane (50 mE) and washed with saturated aqueous solution of NaC1 (50 mE). The organic layer was dried over sodium sulphate, filtered and removed under reduced pressure. The product was purified by flash chromatography using 5% ethyl acetate in hexanes to give title compound (12 g, 85%) as solid. ‘H NMR (400 MHz, CDC13): ö 8.14 (d, J=8.4 Hz, 1H), 7.2 (m, 2H), 3.01 (t, J=6.4 Hz, 2H), 2.68 (t, J=6.0 Hz, 2H), 2.18 (m, 2H); ESI-MS mlz=295 (M+H). |
80% | Trifluoro-methanesulphonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester100. To a solution of 6-hydroxytetralone (2.4 g, 14.8 mmol) in dry DCM (50 mL), cooled to - 10C , was added anhydrous pyridine (1.7 mL, 21 mmol) followed by trifluoro- methanesulphonic anhydride (5.0 g) and the reaction was allowed to warm to r.t. with stirring over 16h. The reaction was quenched with sat. aq. bicarb, and the organic layer separated, washed with water and concentrated under reduced pressure. Purification by flash chromatography using an elution gradient of hexane to 20% EtOAc in hexane gave the title compound in 80% yield: Rf 0.55 (20% EtOAc in hexane); 1H NMR δ (270 MHz, CDCl3) 2.11-2.23 (2H5 m), 2.64-2.69 (2H5 m), 2.98-3.02 (2H5 m), 7.16-7.20 (2H5 m), 8.11 (IH5 d5 J= 9.3 Hz) | |
74% | With pyridine; at 0 - 20℃; | Compound 14 (0.23 g, 1.3 mmol) was dissolved in anhydrous pyridine (3 mL) at 0 C. Then, trifluoromethanesulfonic anhydride (0.26 mL, 1.6 mmol) was carefully added over 1 min, and the reaction mixture was left stirring at r.t for 40 h. Then, water (15 mL) was added, and the aqueous phase was extracted with AcOEt (3 × 5 mL). The combined organic phases were dried over Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography on silica gel (1:4 CH2Cl2:hexane) afforded triflate 15 (0.31 g, 74%) as a colourless oil. IR: 2951, 1689, 1603, 1578, 1482, 1420. 1HNMR (CDCl3) δ: 8.14-8.11 (m, 1H), 7.21-7.18 (m, 2H), 3.01 (t, 2H, J = 6.2), 2.68 (t, 2H, J = 6.6), 2.18 (q, 2H, J = 6.5). Spectroscopic data were coincident with literature. |
74.7% | In pyridine; at 0 - 20℃; | At 0 C, to a solution of 6-hydroxy-3,4-dihydro-2H-naphthalen- 1 -one (55.0 g, 340 mmol, 1.0 eq) in dried pyridine (250 mL) was added Tf20 (115.0 g, 408 mmol, 1.2 eq) dropwise. The mixture was stirred at rt overnight, and then partitioned between water and EtOAc. The organic layers were washed with 2 N HC1 solution, saturated sodium bicarbonate and brine consequently, then dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via flash-chromatography on silica gel (petroleum ether : EtOAc=20: l) to give Trifluoro-methanesulfonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester (74.6 g, 74.7 %) as a light oil. MS ESI calc'd for C11H9F3O4S [M + H] + 295, found 295. |
73% | With triethylamine; In dichloromethane; at 0 - 20℃; for 0.333333h; | 6-HYDROXY-1-TETRALONE (1. 00 g, 6. 17 MMOL), and Et3N (1. 72 mL, 12. 33 MMOL) were dissolved in CH2CI2 (30 mL) at rt. The resulting solution was cooled to 0 C at which time trifluoromethanesulfonic anhydride (1. 56 g, 9. 25 MMOL) was added dropwise. The reaction was stirred for 20 min at which time a solution of saturated NAHC03 was added. The bi- phasic mixture was vigorously stirred for 10 min then diluted with CH2CI2. The organic layer was collected and washed with 1 N HCI and brine. The organic phase was collected, dried over NA2SO4, and filtered. After removal of the solvent under vacuum, the crude oil was purified by silica gel chromatography using 20% EtOAc in Hex as eluent give the 5-oxo- 5, 6, 7, 8-TETRAHYDRO-2-NAPHTHALENYL TRIFLUOROMETHANESULFONATE as a near colorless oil (1. 32 g, 73% yield): 1H NMR (CD2CI2) 6 8. 10 (m, 1H), 7. 23 (m, 2H), 3. 04 (dd, 2H), 2. 68 (dd, 2H), 2. 19 (m, 2H). |
65.2% | With triethylamine; In dichloromethane; at -5 - 25℃; for 4h; | 6-Hydroxy-3,4-dihydronaphthalen-1(2H)-one (11 g, 67.8 mmol) was dissolved in DCM (150 mL)Down to -5 C,Triethylamine (10.3 g, 101.8 mmol) was added dropwise.Slowly drippingTrifluoromethanesulfonic anhydride(23g, 81.5mmol), plus,Move to 25 C for 4 hours.After the reaction is completed, concentrate.The residue was purified by silica gel column chromatography (PE: EA=20:1)Yield: 65.2%). |
36% | With triethylamine; In dichloromethane; at 0 - 20℃; for 12h; | To a solution of Compound 311-1 (2 g, 12 mmol) in DCM (30 mL) was added TEA (1.3 g, 12 mmol) and Tf2O (3.5 g, 12 mmol) at 0C, the resulting mixture was stirred at 20C for 12 hrs. LCMS showed the reaction was completed. Then the reaction mixture was poured into H2O (20 mL) and extracted with DCM (20 mL x 3). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by silica gel chromatography (Ethyl acetate/Petroleum) to give Compound 311-2 (1.3 g, 4.4 mmol, 36% yield) as a yellow gum. M+H+= 294.9 (LCMS),1H NMR (400MHz, CHLOROFORM-d) d= 8.14 (d, J=8.3 Hz, 1H), 7.24 - 7.17 (m, 2H), 3.03 (t, J=6.1 Hz, 2H), 2.75 - 2.63 (m, 2H), 2.23 - 2.12 (m, 2H). |
24% | With triethylamine; In dichloromethane; at 0 - 20℃; for 18h; | To a solution of 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one 1a (5 g, 30.8 mmol) and TEA (3.1 g, 30.8 mmol)in DCM (50 mL) was added Tf2O (8.7 g, 30.8 mmol) at 0C. The mixture was then stirred at RT for 18h. The reactionmixture was washed with water and sat. NaHCO3. The organic layer was dried over Na2SO4 filtered and concentrated.The residue was purified by silica gel column (eluent system B) to afford 5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate1b (2.0 g, colorless liquid), yield: 24.0%1H NMR (400 MHz, CDCl3): δ 8.13 (d , 2H), 7.20-7.15 (m, 2H), 3.05-2.95 (m, 2H), 2.70-2.62 (m, 2H), 2.20-2.10 (m, 2H). |
In pyridine; dichloromethane; at 0 - 20℃; | A) _Preparation of trifluoro-methanesulfonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester To a 1 L round-bottomed flask charged with 6-hydroxy-1-tetralone (Aldrich, 21.97 g, 0.136 mol) at 0 C. was added CH2Cl2 (500 mL) and pyridine (Aldrich, 11 mL, 0.136 mmol). Triflic anhydride (Aldrich, 23 mL, 0.136 mmol) was added through an additional funnel over a period of 12 min. The mixture was gradually warmed to RT and stirred at RT overnight. The residue was diluted with water and two phases were separated. The organic phase was washed with 1 N HCl (100 mL*2), sat NaHCO3, and brine, dried over Na2SO4. After filtration and concentration in vacuo, the crude was purified by flash chromatography (5-11% EtOAc-hexane) to provide the title compound as yellow oil. MS (ESI): 295 (M+H)+. | |
With triethylamine; In dichloromethane; at 0℃; for 0.5h; | 6-Hydroxytetralone (12 g, 0.072 mole) and triethylamine (10 mL, 0.072mole) were dissolved in 200 ml methylene chloride and cooled in an ice bath. Trifluormethanesulfonic anhydride (20 g, 0.072mole) was added dropwise, and the reaction mixture was stirred for 30 minutes. The reaction mixture was poured into 200 mL water, and the organic layer was separated and dried over magnesium sulfate.Evaporation of solvent under reduced pressure gave 15.5 g of trifluoro-methanesulfonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester as an oil. MS: 295 (M+H)+ | |
With pyridine; for 1h; | a) Trifluoro-methanesulfonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester; To a solution of 6-hydroxy-3,4-dihydro-2H-naphthalen-1-one (CASNo. 3470-50-6, 0.10 g, 0.62 mmol) in pyridine (3 ml_) is added trifluoromethane sulfonic anhydride (0.26 g, 0.92 mmol) and the solution is stirred for 1 hour. After dilution with dichloromethane, the solution is washed with water and 1 M aqueous HCI, dried and concentrated to give trifluoro- methanesulfonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester ; 1H NMR (400 MHz, CDCI3) δ ppm 2.15 - 2.24 (m, 2 H), 2.67 - 2.73 (m, 2 H), 3.03 (t, J=6.1 Hz, 2 H), 7.20 - 7.23 (m, 2 H), 8.14 (d, J=8.3 Hz, 1 H). | |
With 4-methyl-morpholine; dmap; In dichloromethane; at -80℃; for 0.0833333h; | Trifluoro-methanesulfonic anhydride (14.35 mL, 77.3 mmol) was added to a CH2Cl2 (150 mL) solution of 6-hydroxy-3,4-dihydro-2H-naphthalen-1-one (11.40 g, 70.3 mmol), N- methylmorpholine (8.5 mL, 77.3 mmol) and DMAP (130 mg, 1 mmol) in 5 min at-80C. The mixture was warmed to 0C in 1 h then poured into a cold solution of saturated NH4Cl. The mixture was diluted with CH2Cl2 (400 mL), washed with H2O, dried over MgSO4, filtered, and concentrated in vacuo to provide the crude compound which was purified by column chromatography (silica, 0 to 60% CH2Cl2 in hexane) to provide the title compound. | |
With pyridine; In dichloromethane; at 0 - 20℃; | To a 1L round-bottomed flask charged with 6-hydroxy-1-tetralone (Aldrich, 21.97 g, 0.136 mol) was added CH2Cl2 (500 mL) and pyridine (Aldrich, 11 mL, 0.136 mol) at 0C. Triflic anhydride (Aldrich, 23 mL, 0.136 mol) was added through an additional funnel over 12 min. The reaction was gradually warmed to RT and stirred overnight. The mixture was treated with water. The organic phase was separated, washed with IN HCl (100 mL x 2), saturated NaHCO3, and brine, dried over Na2SO4, and concentration in vacuo. The crude was purified by flash chromatography (5-11% EtOAc- hexane) to provide the title compound as yellow oil. MS (ESI) : 295 (M+H)+. | |
With pyridine; In dichloromethane; at 0 - 20℃; | To a 1L round-bottomed flask charged with 6-hydroxy-1-tetralone (Aldrich, 21.97 g, 0.136 mol) was added CH2Cl2 (500 mL) and pyridine (Aldrich, 11 mL, 0.136 mol) at 0 C. Triflic anhydride (Aldrich, 23 mL, 0.136 mol) was added through an additional funnel over 12 min. The reaction was gradually warmed to RT and stirred overnight. The mixture was treated with water. The organic phase was separated, washed with 1N HCl (100 mL×2), saturated NaHCO3, and brine, dried over Na2SO4, and concentration in vacuo. The crude was purified by flash chromatography (5-11% EtOAc-hexane) to provide the title compound as yellow oil. MS (ESI): 295 (M+H)+. | |
With 4-methyl-morpholine; dmap; In dichloromethane; at -80 - 0℃; for 65h; | Trifluoro-methanesulfonic anhydride (14.35 mL, 77.3 mmol) was added to a CH2Cl2 (150 mL) solution of 6-hydroxy-3,4-dihydro-2H-naphthalen-1-one (11.40 g, 70.3 mmol), N-methylmorpholine (8.5 mL, 77.3 mmol) and DMAP (130 mg, 1 mmol) in 5 min at -80 C. The mixture was warmed to 0 C. in 1 h then poured into a cold solution of saturated NH4Cl. The mixture was diluted with CH2Cl2 (400 mL), washed with H2O, dried over MgSO4, filtered, and concentrated in vacuo to provide the crude compound which was purified by column chromatography (silica, 0 to 60% CH2Cl2 in hexane) to provide the title compound. | |
With pyridine; In dichloromethane; at 0 - 20℃; | A) Preparation of trifluoro-methanesulfonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester:; To a 1 L round-bottomed flask charged with 6-hydroxy-1-tetralone (Aldrich, 21.97 g, 0.136 mol) at 0 C. was added CH2Cl2 (500 mL) and pyridine (Aldrich, 11 mL, 0.136 mmol). Triflic anhydride (Aldrich, 23 mL, 0.136 mmol) was added though an additional funnel over a period of 12 min. The mixture was gradually warmed to RT and stirred at RT overnight. The residue was diluted with water and two phases were separated. The organic phase was washed with 1N HCl (100 mL×2), sat NaHCO3, and brine, dried over Na2SO4. After filtration and concentration in vacuo, the crude was purified by flash chomatography (5-11% EtOAc-hexane) to provide the title compound as yellow oil. MS (ESI): 295 (M+H)+. | |
With pyridine; In dichloromethane; at 0 - 20℃; | To a 1 -L round-bottomed flask charged with 6-hydroxy- 1 -tetralone (Aldrich, 21.97 g,0.136 mol) at 0 0C was added CH2Cl2 (500 niL) and pyridine (Aldrich, 11 mL, 0.136 mol). Triflic anhydride (Aldrich, 23 mL, 0.136 mol) was added through an additional funnel over a period of 12 min. The reaction mixture was gradually warmed to room temperature and stirred at room temperature overnight. The residue was diluted with water and the two phases were separated. The organic phase was washed with IN HCl (100 mL x 2), saturated NaHCO3, and brine, dried over Na2SO4. After filtration and concentration in vacuo, the crude was purified by flash chromatography (5-11% EtOAc-hexane) to provide the title product as yellow oil. MS (ESI): 295 (M+H)+. | |
With pyridine; In dichloromethane; at 0 - 20℃; under 760.051 Torr; | Reference 2; Synthesis of (/?)-6-(l -piperidin- 1 -ylmethylvinyl)- 1 ,2,3 ,4-tetrahydronaphthalen- 1 -ylamine; Step A: Synthesis of trifiuoromethanesulfonic acid 5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl ester; To a 1-L round-bottomed flask charged with 6-hydroxy-l-tetralone (Aldrich, 21.97 g, 0.136 mol) at 0 C was added CH2Cl2 (500 mL) and pyridine (Aldrich, 11 mL, 0.136 mol). Triflic anhydride (Aldrich, 23 mL, 0.136 mol) was added through an additional funnel over a period of 12 min. The reaction mixture was gradually warmed to room temperature and stirred at room temperature overnight. The residue was diluted with water and the two phases were separated. The organic phase was washed with IN HCl (100 mL x 2), saturated NaHCO3, and brine, dried over Na2SO4. After filtration and concentration in vacuo, the crude was purified by flash chromatography (5-1 1% EtOAc-hexane) to provide the title product as yellow oil. MS (ESI): 295 (M+H)+. | |
With 2,6-dimethylpyridine; dmap; In dichloromethane; at -40 - 25℃; for 3h;Inert atmosphere; | To a solution of 6-hydroxytetralin-1-one (45 g, CAS 3470-50-6), N,Ndimethylaminopyridine (“DMAP”, 6.8 g) and 2,6-lutidine (35.7 g) in CH2Cl2 (1 .6 L) at -40c was added triflic anhydride (uTf2Ou, 55.2 mL) dropwise under N2. The reactionwas stirred at r.t. for 3 h, and quenched with 5% saturated aqueous NaHCO3 solution. The aqueous layer was extracted with CH2CI2 (3x 800 mL), and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The obtained product (82 g) was used in the next step (step 2) without any further purification.1H NMR (400 MHz, CDCI3): 8.16 (d, 1H), 7.24-7.22 (m, 2H), 3.06-3.03 (m, 2H), 2.73-2.70 (m, 2H), 2.24-2.18 (m, 2H). | |
With pyridine; In dichloromethane; at 25℃; for 1h; | <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (5 g, 30.2 mmol) was suspended in DCM (50 ml). Pyridine (18.08 ml, 224 mmol) was added followed by trifluoromethane sulfonic anhydride (12.79 g, 45.3 mmol), keeping the temperature below 25 C. using an ice bath. After 1 h the reaction solution was quenched by addition of 300 ml of 0.1 M aqueous copper (II) sulfate. The organic layer was separated and washed with brine (5 ml), dried over Na2SO4 and concentrated in vacuo to give the title compound as orange oil. LC-MS: Rt 2.32 min; no mass detected; method A | |
With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 1h; | Step A.; Methyl 5-oxo-5,6,7,8-tetxahydronaphthalene-2-carboxylateTo a solution of 6-hydroxy 1-tetralone (3.7 g, 22.7 mmol) and 2,6-lutidine (12.2 mL, 102.5 mmol) in dry CH2Cl2 (50 mL) at 0 0C was slowly added triflic anhydride (4.0 mL, 34.0 mmol) and the reaction mixture was stirred at 0 0C for Ih. H2O (50 mL) was then added to quench the reaction. After stirring for 15 min at room temperature, the mixture was diluted with CH2Cl2 (100 mL) and the layers were separated. The organic layer was washed once with 10% aqueous NaHCO3 solution (100 mL), once with brine (100 mL), dried over Na2SO4, filtered and concentrated. Chromatography (5% to 8% EtOAc in Hexane) gave 6-triflate 1-tetralone. HPLC/MS: m/z = 295.1 (M+l), R4 = 3.54 min. 1H NMR (CDCl3): δ 8.17 (IH, d, J= 8.50 Hz), 7.26-7.23 (2H, m), 3.06 (2H, t, J= 6.0 Hz), 2.73 (2H, t, J= 6.0 Hz), 2.22 (2H, qn, J = 6.0 Hz).A mixture of 6-triflate 1-tetralone (4.8 g, 16.3 mmol), Et3N (4.5 mL, 32.6 mmol), Pd(OAc)2 (0.11 g, 0.49 mmol) and dppf (0.54 g, 0.98 mmol) in dry MeOH (10 mL) was purged with carbon monoxide for 5 min and then stirred under a CO balloon at 60 0C for 2 h. The reaction mixture was allowed to cool to room temperature, diluted with brine (100 mL) and extraction with Et2O (3 x 50 mL). The combined organic layers were washed once with IN aqueous HCl, once with brine, dried over Na2SO4, filtered and concentrated. Chromatography (8% EtOAc in Hexane) afforded methyl 5-oxo- 5,6,7,8-tetrahydronaphthalene-2-carboxylate as a white solid. HPLC/MS: m/z = 205.1 (M+l), R1 = 3.01 min. 1H NMR (CDCl3): δ 8.08 (IH, d, J= 8.0 Hz), 7.95 (IH, s), 7.94 (IH, d, J= 8.0 Hz), 3.96 (3H, s), 3.04 (2H, t, J= 6.0 Hz), 2.71 (2H, t, J= 6.0 Hz), 2.18 (2H, qn, J= 6.0 Hz). | |
With triethylamine; In dichloromethane; at 0℃; for 0.5h; | Example 14 i^-(6-Benzenesulfonyl-l,2,3,4-tetrahvdro-naphthalen-l-ylmethyl)-methylamine The synthetic procedure described in this Example was carried out according to the process shown in Scheme S. <n="63"/>2EtH, 3 HSCHEME SStep 1Trifluoro-methanesulfonic acid 5-oxo-5,6,7,8-tetrahvdro-naphthalen-2-yl ester 6-Hydroxytetralone (12 g, 0.072 mole) and triethylamine (10 mL, 0.072mole) were dissolved in 200 ml methylene chloride and cooled in an ice bath.Trifluormethanesulfonic anhydride (20 g, 0.072mole) was added dropwise, and the reaction mixture was stirred for 30 minutes. The reaction mixture was poured into 200 mL water, and the organic layer was separated and dried over magnesium sulfate. Evaporation of solvent under reduced pressure gave 15.5 g of trifluoro-methanesulfonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester as an oil. MS: 295 (M+H)+' | |
With 2,6-dimethylpyridine; In dichloromethane; at 0℃; | 1. To a stirred solution of 6-hydroxy-1-tetralone (3 g, 0.0184 mol) and 2,6-Lutidine (9.6 ml, 0.082 mol,4.5 eq.) in DCM (48 ml) at O0C was added slowly Triflic anhydride (4.5 ml, 0.0274mol,1.5 eq.) and the reaction mixture was stirred for 1 h at O0C. Water (48 ml) was added to quench the reaction. After stirring for 15 min at RT the mixture was diluted with DCM (96 ml) and the layer were separated. The organic layer was washed with 10 % aqueous NaHCθ3 solution (100 ml), water (100 ml) and then brine (50 ml). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100-200) The product is eluted in 2 %ethyl acetate/hexane. | |
With triethylamine; In dichloromethane; at -78 - 0℃; for 1h; | To a solution of 6-hydroxy-3,4-dihydronapbthalen-1(2H)-one (2.0 g) in dichloromethane (20 mL), triethylamine (5.16 mL) and trifluoromethanesulfonic anhydride (2.49 mL) were added at -78C, followed by stirring at 0C for 1 hour. After adding a saturated aqueous sodium hydrogencarbonate solution, the mixture was stirred and extracted with diethyl ether. The organic layer was successively washed with 1 N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, dried and concentrated. The residue thus obtained was purified by silica gel column chromatography (hexane: ethyl acetate =9:1) to thereby give the title compound (2.34 g) having the following physical properties. TLC: Rf 0.34 (hexane: ethyl acetate = 85: 15). | |
With pyridine; In dichloromethane; at 0 - 10℃; for 0.5h; | A reactor was charged with EX-24 (1.0 equiv., scaling factor) and dichloromethane (15 volumes). The mixture was cooled to about 0 C, and pyridine (1.4 equiv.) was charged to the reactor. Triflic anhydride (1.2 equiv.) was then charged while maintaining an internal temperature below about 10 C. The reaction mixture was agitated at about 0 C for about 30 min, and then quenched by charging a saturated aqueous sodium carbonate solution (10 volumes) and mixing the biphasic mixture for about 5 min. The mixture was adjusted to about 20 C, and the organic layer was separated, washed with water (10 volumes), dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography using ethyl acetate and hexanes to afford EX-25.1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 8.4 Hz, 1H), 7.18-7.27 (m, 2H), 3.04 (t, J = 6.1 Hz, 2H), 2.67-2.75 (m, 2H), 2.15-2.26 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.8% | With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2.5h; | Dissolve 6-hydroxy-1-tetralone (M-10, 2.92g, 18.0mmol) in DMF (40mL), and then add N-(2-chloroethyl)morpholine hydrochloride (3.52g , 18.9mmol) and Cs2CO3 (7.63g, 23.4mmol), react at 100C for 2.5h. H2O (50 mL) was added to the reaction solution, extracted with DCM (100 mL×3), the organic phases were combined, washed with saturated NaCl, dried with anhydrous Na2SO4, and concentrated to obtain a yellow solid M-11 (4.45 g, 89.8%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1H-imidazole; In DMF (N,N-dimethyl-formamide); at 20℃; for 18h; | To a 250 mL round-bottomed flask equipped with magnetic stirring were added 6-hydroxy-1-tetralone (5.7 g, 35 mmol, Aldrich), imidazole (6 g, 88 mmol, Aldrich), and chloro-tert-butyldimethylsilane (6.3 g, 42 mmol, Aldrich) in DMF (40 mL). After stirring for ca. 18 h at RT, ether (500 mL) was added, and the organic layer was washed with 1 M HCl and brine (4x), dried over MgSO4, filtered and concentrated in vacuo. The crude was purified on a Biotage silica gel column using 20 : 1 hexane-EtOAc as the eluant. The desired compound was isolated as a tan oil (ESI-MS, + ion, M/Z = 277 (MH+)). | |
With 1H-imidazole; In DMF (N,N-dimethyl-formamide); at 20℃; for 18h; | To a 250 mL round-bottomed flask equipped with magnetic stirring were added 6-hydroxy-1-tetralone (5.7 g, 35 mmol, Aldrich), imidazole (6 g, 88 mmol, Aldrich), and chloro-tert-butyldimethylsilane (6.3 g, 42 mmol, Aldrich) in DMF (40 mL). After stirring for ca. 18 h at RT, ether (500 mL) was added, and the organic layer was washed with 1 M HCl and brine (4×), dried over MgSO4, filtered and concentrated in vacuo. The crude was purified on a Biotage silica gel column using 20:1 hexane-EtOAc as the eluant. The desired compound was isolated as a tan oil (ESI-MS, + ion, m/z=277 (MH+)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
69% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
61% | With potassium carbonate; In acetonitrile;Reflux; | To a solution of6-hydroxy-3,4-dihydro-1(2H)-naphthalenone (2.0 g, 12.3 mmol) and (2-bromoethyl)benzene (4.8 g, 25.8 mmol) inACN (20 mL) was added potassium carbonate (3.4 g, 24.6 mmol) at rt. The solution was heated at reflux overnight. The reaction was filtered, concentrated, and purified by silica gelchromatography (PE/EtOAc/DCM = 10:1:2) to give 2.0 g (61%) of the title compound as a brown oil. 1H NMR (300 MHz, CDCh): 8 2.08-2.16 (2H, m), 2.62 (2H, t, J = 6.3 Hz),2.92 (2H, t, J = 6.3 Hz), 3.13 (2H, t, J = 7.2 Hz), 2.92 (2H, t, J = 7.2 Hz), 6.71 (1H, d, J= 2.1 Hz), 6.83 (1H, dd, J = 2.4, 8.7 Hz), 7.27-7.38 (5H, m), 8.01 (1H, dd, J = 8.7 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone;Heating / reflux; | 3.30 ml of allyl bromide was added to a mixture consisting of 5.62 g of 6-hydroxy-3,4-dihydroxynaphthalen-1(2H)-one, 5.27 g of potassium carbonate, and 60 ml of acetone. The obtained mixture was heated to reflux under nitrogen atmosphere overnight. The reaction solution was cooled to a room temperature, and the precipitate was removed by filtration. The solvent was removed under a reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate), so as to obtain 6.35 g of the subject compound. 1H-NMR (CDCl3) δ (ppm): 2.08-2.15 (m, 2H), 2.59-2.62 (m, 2H), 2.92 (t, J=6.0 Hz, 2H), 4.58-4.60 (m, 2H), 5.30-5.34 (m, 1H), 5.40-5.45 (m, 1H), 6.00-6.10 (m, 1H), 6.72 (d, J=2.6 Hz, 1H), 6.84 (dd, J=2.4, 8.8 Hz, 1H), 8.00 (d, J=8.8 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: 6-Hydroxy-1-tetralone (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
97% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: 6-Hydroxy-1-tetralone (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. 6-(Benzyloxy)-3,4-dihydronaphthalen-1(2H)-one (6a) The title compound was prepared in a yield of 97%: mp 100.9-102.1 C (cyclohexane). 1H NMR (BrukerAvance III 600, CDCl3) delta 2.09 (p, J = 6.5 Hz, 2H), 2.56 - 2.61 (m, 2H), 2.90 (t, J = 6.1 Hz, 2H), 5.09 (s,2H), 6.77 (d, J = 2.2 Hz, 1H), 6.88 (dd, J = 8.7, 2.6 Hz, 1H), 7.30 - 7.36 (m, 1H), 7.36 - 7.43 (m, 4H),8.00 (d, J = 8.7 Hz, 1H); 13C NMR (Bruker Avance III 600, CDCl3) delta 23.29, 30.10, 38.85, 69.20, 113.53,113.58, 122.11, 126.64, 128.99, 129.67, 131.78, 135.20, 146.94, 162.30, 197.08; APCI-HRMS m/z: calcdfor C17H17O2 (MH+), 253.1223, found 253.1220. |
94% | With potassium carbonate; In acetonitrile; at 50℃; for 2h; | Step 1: Preparation of 6-benzyloxytetralin-1-one To a solution of 6-hydroxytetralin-l-one (100 g, 616.56 mmol, 1.00 eq) in acetonitrile (1000 mL) was added potassium carbonate (170.43 g, 1.23 mol, 2.00 eq) and benzyl bromide (126.54 g, 739.87 mmol, 88 mL, 1.20 eq). The reaction mixture was stirred at 50 C. for 2 hours. TLC (petroleum ether:ethyl acetate=5:1) showed most of the starting material was consumed. Water (1000 mL) was added to the mixture, the resulting mixture was extracted with ethyl acetate (600 mL*3). The combined organic phase was washed with brine (800 mL), dried over sodium sulfate, filtered and concentrated in vacuum. The residue was triturated with petroleum ether and ethyl acetate (303 mL, petroleum ether:ethyl acetate=100:1, V:V). The mixture was filtered and the filter cake was washed with petroleum ether (50 mL*2), dried in vacuum to give 6-benzyloxytetralin-1-one (146 g, 578.65 mmol, 94% yield) as a brown solid. 1H-NMR (400 MHz, CDCl3) delta 8.02 (d, J=8.8 Hz, 1H), 7.45-7.34 (m, 5H), 6.91 (dd, J=8.8, 2.4 Hz, 1H), 6.80 (d, J=2.4 Hz, 1H), 5.12 (s, 2H), 2.93 (t, J=6.0 Hz, 2H), 2.62 (t, J=6.4 Hz, 2H), 2.15-2.09 (m, 2H). |
84% | With potassium carbonate; In acetonitrile; at 15℃; for 3h; | Step 1: 6-(Benzyloxy)-3,4-dihydronaphthalen-1(2H)-one 129a To a mixture of 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one 101f (20.0 g, 123.31 mmol) and benzyl bromide (20 mL, 246.62 mmol) in MeCN (70 mL) was added K2CO3 (33.2 g, 240.21 mmol) at 15 C. and the resulting mixture was stirred for 3 hours. The mixture was filtered, concentrated and the residue was purified by flash column chromatography eluted with 0-10% EtOAc in petroleum ether to afford 129a (26 g, 84% yield) as brown oil. 1H NMR (400 MHz, CDCl3) delta 8.06-7.98 (m, 1H), 7.46-7.32 (m, 5H), 6.90 (d, J=8.8 Hz, 1H), 6.80 (s, 1H), 5.16-5.08 (m, 2H), 2.93 (t, J=6.0 Hz, 2H), 2.62 (t, J=6.4 Hz, 2H), 2.17-2.06 (m, 2H). |
80% | With potassium carbonate; In acetone;Inert atmosphere of nitrogen; Heating; Reflux; | The mixture of 6-hydroxy-3,4-dihydro-2H-naphthalen-l-one (30.74 g, 0.1895 mol), benzyl bromide (27.0 mL, 0.227 mol) and potassium carbonate (39.3 g, 0.284 mol) in acetone (250 mL, 3.4 mol) was heated to reflux under an atmosphere of nitrogen for 3 hours. The mixture was cooled to 10 C with an ice bath, filtered and washed with small amount of acetone. The filtrate was concentrated in rotavap. The resulting crystals were collected by filtration and washed with EtOAc-hexane then hexane to give a pale yellow solid product as the first crop. The mother liquid was concentrated in rotavapor and the residue was purified by chromatograph with EtOAc:hexane (0:100 to 20:80) to give the second crop of solid product (38.07g, 80%). 1H NMR (CHLOROFORM-d) delta: 8.02 (d, J = 8.6 Hz, IH), 7.32 - 7.51 (m, 5H), 6.91 (dd, J = 8.8, 2.3 Hz, IH), 6.80 (s, IH), 5.13 (s, 2H), 2.93 (t, J = 6.1 Hz, 2H), 2.56 - 2.68 (m, 2H), 2.12 (quin, J = 6.3 Hz5 2H). MS (M+l): 253.0. |
With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 4h; | A suspension of 6-methoxy-1-tetralone (99 g) in 48% hydrobromic acid (800 ml) was stirred overnight at 120C. The reaction mixture was poured into ice water, the resulting solid was sequentially washed with water and hexane-diethyl ether system. To a solution of the resulting 6-hydroxy-3,4-dihydro-2H-naphthalen-1-one (76 g) in. N,N-dimethylformamide (400 ml) were sequentially added potassium carbonate (76 g) and benzyl bromide (59 ml), and the solution was stirred for 4 hours at room temperature. The reaction mixture was poured into water, the resulting solid was sequentially washed with water and hexane-diethyl ether system to provide the title compound (110 g).1H-NMR (400MHz, CDCl3); delta (ppm): 2.12 (pent, 2H), 2.61 (t, 2H), 2.92 (t, 2H), 5.12 (s, 2H), 6.79 (d, 1H), 6.90 (dd, 1H), 7.32-7.45 (m, 5H), 8.01 (d, 1H). | |
With potassium carbonate; In acetone; at 20 - 40℃; for 3.5h; | Procedure (1): To a solution of 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one (24.3 g) in acetone (160 mL), benzyl bromide (29.4 mL) and potassium carbonate (31.1 g) were added at room temperature, followed by stirring at 40C for 3.5 hours. After filtering off the insoluble matters and concentrating the filtrate, the residue was washed with a mixed solvent of tert-butyl methyl ether-hexane (1:4) to thereby give 6-(benzyloxy)-3,4-dihydronaphthalen-1(2H)-one (34.5 g). | |
With potassium carbonate; In [(2)H6]acetone; hexane; | Example 104 6-(Benzyloxy)-3,4-dihydronaphthalen-1(2H)-one The mixture of 6-hydroxy-3,4-dihydro-2H-naphthalen-1-one (30.74 g, 0.1895 mol), benzyl bromide (27.0 mL, 0.227 mol) and potassium carbonate (39.3 g, 0.284 mol) in acetone (250 mL, 3.4 mol) was heated to reflux under an atmosphere of nitrogen for 3 hours. The mixture was cooled to 10 C. with an ice bath, filtered and washed with small amount of to acetone. The filtrate was concentrated in rotavap. The resulting crystals were collected by filtration and washed with EtOAc-hexane then hexane to give a pale yellow solid product as the first crop. The mother liquid was concentrated in rotavapor and the residue was purified by chromatograph with EtOAc:hexane (0:100 to 20:80) to give the second crop of solid product (38.07 g, 80%). 1H NMR (CHLOROFORM-d) delta: 8.02 (d, J=8.6 Hz, 1H), 7.32-7.51 (m, 5H), is 6.91 (dd, J=8.8, 2.3 Hz, 1H), 6.80 (s, 1H), 5.13 (s, 2H), 2.93 (t, J=6.1 Hz, 2H), 2.56-2.68 (m, 2H), 2.12 (quin, J=6.3 Hz, 2H). MS (M+1): 253.0. | |
34.5g | With potassium carbonate; In acetone; at 40℃; for 3.5h; | To a solution of 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one (CAS registry number: 3470-50-6) (24.3 g) inacetone (160 mL), benzyl bromide (29.4 mL) and potassium carbonate (31.1 g) were added at room temperature andthe mixture was stirred at 40C for 3.5 hours. After insoluble matters were filtered off, the mixture was concentrated andwashed with a mixed solvent of tert-butyl methyl ether (MTBE)-hexane (1 : 4) to give the title compound (34.5 g) havingthe following physical property.TLC: Rf 0.38 (hexane : ethyl acetate = 3 : 1). |
With potassium carbonate; In acetone; at 20 - 40℃; for 3.5h; | To a solution of 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one (24.3 g) in acetone (160 mL), benzyl bromide (29.4 mL) and potassium carbonate (31.1 g) were added at room temperature, followed by stirring at 40C for 3.5 hours. After filtering off the insoluble matters and concentrating the mixture, the residue was washed with a mixed solvent of tert-butyl methyl ether - hexane (1: 4) to thereby give the title compound (34.5 g) having the following physical properties. TLC: Rf 0.38 (hexane: ethyl acetate =3:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6-hydroxytetralone (200 mg, 1.23 mmol, 1.0 eq.) was dissolved in 3 mL dMF in a 25 mL round-bottom flask and the flask immersed in an ice bath at 0 C. Under stirring, sodium hydride (60 mg, 1.5 mmol, 1.2 eq.) was added and 10 min later the addition was made of chloromethyl methyl ether (0.14 mL, 1.85 mmol, 1.5 eq.). The mixture was stirred at ambient temperature for 2 hours. On completion of the reaction, the mixture was diluted with 90 mL acOEt and washed with 3×70 mL water. The organic phase was washed with saturated aqueous NaCl solution (20 mL) and dried over MgSO4. after filtration, the solvent was evaporated and the residue purified by silica gel chromatography (gradient 100 to 70% PE and 0 to 30% aE/). Product 102 was obtained in the form of a colourless oil (248 mg, 98%). R (petroleum ether/acOEt 50:50) 0.90. 1H NMR (400 MHz, CdCl3) δ 790 (d, J=87 Hz 1H), 685 (dd, J=8.7, 2.5 Hz, 1H), 6.78 (d, J=2.5 Hz, 1H), 5.14 (s, 2H), 3.40 (s, 3H), 2.3 (t, J=6.0 Hz, 2H), 2.51 (t, J=6.0 Hz, 2H), 2.02 (quin, J=6.0 Hz, 2H). 13C NMR (101 MHz, CdCl3) δ 196.9, 161.0, 146.7, 129.3, 126.9, 114.7, 114.6, 93.8, 56.1, 38.8, 29.9, 23.2. IR (diamond aTR cm-1) ν 2942, 2828, 1672, 1570, 1491, 1080, 920, 826. HRMS (EI-MS): m/z calculated for C12H14N4NaO3 [M+Na]+: 229.0835, found: 229.0833. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With pyridinium p-toluenesulfonate; In dichloromethane; for 84h; | 6-Hydroxytetralone 25 (2.0 g; 12.3 mmol) was suspended in dichloromethane (100 mL) and stirred in the presence of 3, 4-dihydropyran (3.11 g; 37 mmol ; 3.38 mL) and PPTS (100 mg) for 3.5 days. The organic layer was washed with water and brine and dried [(NA2S04).] The solid remaining after removing the solvent was purified by flash chromatography (ether/hexane; 20: 80) to give the tetrahydropyran 26 as an off-white solid (2.67 g; 88%). |
Yield | Reaction Conditions | Operation in experiment |
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73% | With potassium carbonate; In acetonitrile; for 14h;Heating / reflux; | In a 500 mL round bottom flask, 6-hydroxy-3,4-dihydro-2H-naphthalen-1-one (10 g, 61.0 mmol), 1-bromo-3-chloro-propane (9.6 g, 61.0 mmol), and potassium carbonate (9.3 g, 67.1 mmol) in acetonitrile (300 mL) was heated to reflux 14 h. The reaction was cooled and the solvent concentrated under vacuum. The slurry was partitioned between methylene chloride and water, separated, dried over MgSO4. Purification with silica gel chromatography eluting with hexanes/ethyl acetate (3:1) produced 10.6 g (73%). Mp 85-87 C. MS m/z 239 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
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100% | With pyridine; at 20℃; for 3h; | Step 1: 5-Oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate To a solution of 6-hydroxy-3,4-dihydro-2H-naphthalen-1-one (6.3 g, 39.1 mmol) in dry pyridine (30 mL) at 0 C. was added trifluoromethanesulfonic anhydride (7.3 mL, 43.0 mmol) over a few minutes. The solution was warmed to room temperature and stirred for 3 h. The reaction was poured into 1N HCl and diluted with ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate (11.5 g, 100%). The crude product was used without purification. MS (ES) m/z 295 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
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6% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 20℃; | 6-Hydroxy-tetralone (0.48 g, 0.003 mol) is dissolved in tetrahydrofuran (30 ML).triphenylphosphine (1.11 g, 0.0042 mol) is then added followed by the product from step 5, 2-[3-(4-methoxy-3-methyl-benzyl)-3H-imidazol-4-yl]-ethanol (0.75 g, 0.003 mol).A solution of diethyl azodicarboxylate (0.6 ML, 0.0038 mol) in tetrahydrofuran (10 ML) is added slowly under a nitrogen atmosphere.The reaction is stirred at room temperature overnight under a nitrogen atmosphere.The precipitate is filtered, and the filtrate concentrated in vacuo.The residue is taken up in ethyl acetate, washed three times with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo.The product is purified by flash chromatography (5% methanol in chloroform) to give 0.51 g (43% yield) material which is further purified by reverse phase HPLC (C-18 column; 22*250 mm; 0.1 mm; 300 Å; gradient: 10% to 40% acetonitrile; 0.1% trifluoroacetic acid; against 1% aqueous trifluoroacetic acid; 100 minutes; 13 ML/minute), to give 0.070 g of Compound 12 (6% yield). MS: APCI: M+1: 391.2 (M: 390.5). Analysis calculated for C24H26N2O3.1.25 CF3COOH: C, 59.72; H, 5.15; N, 5.26. Found: C, 59.71; H, 5.13; N, 5.19. |
Yield | Reaction Conditions | Operation in experiment |
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82% | Combine 6-Hydroxytetralone (4.42g, 27.24 mniol), 4-Fluorobenzonitrile (3 .Og, 24.76 mmol), K2C03 (5.lg, 37.14 mmol)and toluene/DMA (3Ornl/9Oml), then reflux under nitrogen using a Dean Stark Trap. After 4 hours, cool the reaction to room temperature and add to a separatory funnel. Add Ethyl acetate and wash the organic layer several times with water, then a brine solution, and dry the organic layer over Na2SO4. Flash chromatograph using 4/1 hexanes/ethyl acetate eluant to afford 5.34 g, 20.3 mmol (82% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 2.1-2.2 (2H, m), 2.6-2.7 (2H, m), 2.9-3.0 (2H, m), 6.85 (1H, s), 6.9-7.0 (1H, m), 7.05-7.15 (2H, m), 7.6-7.7 (2H, rn), 8.05-8.10 (1H, m); MS m/z 264 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
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With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0 - 20℃; | To a mixture of 6-HYDROXY-1-TETRALONE (Aldrich, 1.0 g, 6.17 mmol, 1.0 eq), N, N-dimethylethanolamine (Aldrich, 0. 93 mL, 9.26 mmol, 1.5 eq), and TRIPHENYLPHOSPHINE (Aldrich, 2.43 g, 9.26 mmol, 1.5 eq) in THF (10 mL) was added diethyl AZODICARBOXYLATE (Aldrich, 1.94 mL, 12.34 mmol, 2.0 eq) at 0 C. The reaction mixture was gradually warmed to RT and continued to stir overnight. The solvent was evaporated in vacuo. The residue was purified by silica gel chromatography (3%-5% MEOH-CH2CL2) to provide the product as orange oil. MS (ESI): 234 (M+H) +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 50℃; for 17h; | 1.1 g OF METHANESULFONIC ACID 3- [2, 6-DICHLORO-4- (3, 3-DICHLORO-ALLYLOXY)-PHENOXY]- propyl ester, 1.1 g of potassium carbonate and 0.45 G OF 6-HYDROXY-1-TETRALONE ARE stirred in 10 ml of dimethylformamide at 50C for 17 hours. The reaction mixture is poured into water and extracted with ethyl acetate. After concentration of the organic phases and purification over silica gel, 6- {3- [2, 6-DICHLORO-4- (3, 3-DICHLORO-ALLYLOXY)-PHENOXY]-PROPOXY}-3, 4-dihydro-2H- NAPHTHALEN-1-ONE is obtained. |
Yield | Reaction Conditions | Operation in experiment |
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22% | With hydrogenchloride; lithium hexamethyldisilazane; In tetrahydrofuran; water; | Example 5 ethyl (6-hydroxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)(oxo)acetate To 6-hydroxy-1-tetralone (10.4 g, 0.064 mol) and ethyl oxalate (17.4 mL, 0.128 mol) in THF (100 mL) was added dropwise lithium bis(trimethylsilyl)amide (1M in THF, 130 mL). The slurry was stirred overnight and a solid was filtered. The solid was dissolved in water and made acidic to pH 2.5 with 3 N HCl, precipitating a waxy solid. The waxy solid was extracted into EtOAc, dried (MgSO4), and concentrated in vacuo leaving a dark solid (15.7 g). The solid was purified by chromatography on silica gel, eluding with 15% EtOAc/hexanes to give a yellow solid (5.9 g). The solid was recrystallized from EtOAc/hexanes to give the product as a yellow solid, 3.7 g (22% yield). FABHRMS m/z 263.0925 (M+H, C14H15O5 requires 263.0919). 1H NMR (CDCl3/300 MHz) 7.93 (d, 1H); 6.80 (d of d, 1H); 6.68 (s, 1H); 5.72 (s, 1H); 4.39 (q, 2H); 3.00-2.75 (m, 4H); 1.40 (t, 3H). Anal. Calcd for C14H14O5: C, 64.12; H, 5.38. Found: C, 63.79; H, 5.35. |
Yield | Reaction Conditions | Operation in experiment |
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96% | With potassium carbonate; | Reference Example 66 A mixture of 4-chloromethyl-5-methyl-2-phenyloxazole (19.2 g), 6-hydroxytetralone (15.0 g), potassium carbonate (15.4 g) and dimethylformamide (DMF) (100 ml) was stirred at 80 to 90 C. for 2 hours. The reaction mixture was poured into water, and the precipitated crystals of 6-(5-methyl-2-phenyl-4-oxazolylmethoxy)tetralone (29.5 g, 96%) were collected by filtration and recrystallized from dichloromethane-methanol. Colorless prisms, mp: 143-144 C. |
Yield | Reaction Conditions | Operation in experiment |
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91.5% | With potassium carbonate; In hydrogenchloride; acetone; | b 6-n-butoxy-1-tetralone A solution of 2.50 g of 6-hydroxy-1-tetralone in 20 ml of acetone, 2.54 g of potassium carbonate and 2 ml of 1-bromobutane were heated under reflux for four days. After evaporation the residue was diluted carefully in 20 ml of 1N hydrochloric acid and extracted three times with ethyl acetate. Then the extracts were washed with aqueous saturated solutions of sodium hydrogen carbonate and sodium chloride and dried over sodium sulfate. After evaporation the resulting residue was purified by chromatography with diethyl ether/petroleum ether (1:2) to yield 3.08 g (91.5% of the theoretical yield) of 6-n-butoxy-1-tetralone in the form of a nearly colorless oil. 1 H-NMR (CDCl3): 0.96-1.01 (t, 3H, CH3); 1.43-1.56 (m, 2H, CH2); 1.73-1.83 (m, 2H, CH2); 2.07-2.15 (m, 2H, CH2); 2.58-2.63 (t, 2H, CH2); 2.89-2.94 (t, 2H, CH2); 3.99-4.03 (t, 2H, OCH2); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84.7% | In acetic acid; | The starting material was prepared as follows: A mixture of 6-methoxy-1-tetralone (5 g, 28.4 mmol) in acetic acid (50 ml) and 48% bromhydric acid (25 ml) was heated at reflux for 7 hours. After extraction with CH2 Cl2 and evaporation, the residue was purified by flash chromatography (AcoEt/petroleum ether 45/55) to give 6-hydroxy-1-tetralone as a foam (3.9 g; 84.7%). 1 H-NMR (DMSO-d6) δ: 1.95-2 (m, 2H); 2.46-2.52 (m, 2H); 2.83 (t, 2H); 6.64 (d, 1H); 6.70 (dd, 1H); 7.73 (d, 1H). |
84.7% | In acetic acid; | The starting material was prepared as follows: A mixture of 6-methoxy-1-tetralone (5 g, 28.4 mmol) in acetic acid (50 ml) and 48% bromhydric acid (25 ml) was heated at reflux for 7 hours. After extraction with CH2Cl2 and evaporation, the residue was purified by flash chromatography (AcoEt/petroleum ether 45/55) to give 6-hydroxy-1-tetralone as a foam (3.9 g; 84.7%). 1H-NMR (DMSO-d6) δ: 1.95-2 (m, 2H); 2.46-2.52 (m, 2H); 2.83 (t, 2H); 6.64 (d, 1H); 6.70 (dd, 1H); 7.73 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; NaH;AlCl3; In N-methyl-acetamide; methanol; cyclohexane; N,N-dimethyl-formamide; mineral oil; | EXAMPLE 31 6-Thiomethyl1-tetralone 6-Hydroxy- 1-tetralone (16.2 g) prepared from 6-methoxy1-tetralone and AlCl3, was dissolved in dry dimethylformamide (DMF)(50 ml) and added dropwise to a suspension of 4 g NaH (60% in mineral oil) and dry DMF (200 ml) over 30 min. Then, dimethylthiocarbamyl chloride (14.8 g) was added and the reaction heated at 85 C. for, 4 hrs. The reaction was poured onto ice and extracted with CH2 Cl2 (150 ml). The CH2 Cl2 layer was washed with 10% aq. NaOH, then saturated NaCl solution. The organic layer was separated, dried (Na2 SO4), filtered and evaporated giving a tan solid (18.1 g). This was added to mineral oil (100 ml) and heated at 270 C. for 2 hrs, then cooled. Cyclohexane (500 ml) was added and a solid separated (14.3 g). This product was added to NaOH (10 g) and MeOH (150 ml) and refluxed 2 hrs. The reaction was cooled, then methyliodide (9.94 g) was added followed by refluxing for 2 hrs. | |
With sodium hydroxide; NaH;AlCl3; In N-methyl-acetamide; methanol; cyclohexane; N,N-dimethyl-formamide; mineral oil; | EXAMPLE 31 6-Thiomethyl-1-tetralone 6-Hydroxy-1-tetralone (16.2 g) prepared from 6-methoxy 1-tetralone and AlCl3, was dissolved in dry dimethylformamide (DMF)(50 ml) and added dropwise to a suspension of 4 g NaH (60% in mineral oil) and dry DMF (200 ml) over 30 min. Then, dimethylthiocarbamyl chloride (14.8 g) was added and the reaction heated at 85 C. for 4 hrs. The reaction was poured onto ice and extracted with CH2 Cl2 (150 ml). The CH2 Cl2 layer was washed with 10% aq. NaOH, then saturated NaCl solution. The organic layer was separated, dried (Na2 SO4), filtered and evaporated giving a tan solid (18.1 g). This was added to mineral oil (100 ml) and heated at 270 C. for 2 hrs, then cooled. Cyclohexane (500 ml) was added and a solid separated (14.3 g). This product was added to NaOH (10 g) and MeOH (150 ml) and refluxed 2 hrs. The reaction was cooled, then methyliodide (9.94 g) was added followed by refluxing for 2 hrs. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N-methyl-acetamide; dichloromethane; | Step 1. 6-(3-N-Phthalimidopropoxy)-1-tetralone. 77.5 g of N-bromopropylphthalimide are added to a stirred solution of 6-hydroxy-1-tetralone (48.6 g) and potassium carbonate (39.9 g) in dimethylformamide (480 ml). The reaction mixture is stirred at RT overnight, and then poured into a stirred mixture of H2 O and methylene chloride. The layers are separated and the aqueous portion washed with methylene chloride. The combined methylene chloride fractions are washed with H2 O, dried over sodium sulfate, filtered and the filtrate evaporated in vacuo, yielding an off-white solid which is recrystallized from absolute ethanol, yielding 73.1 g of crystals, M.P. 143-145 C. | |
With potassium carbonate; In N-methyl-acetamide; dichloromethane; | Step 1. 6-(3-N-Phthalimidopropoxy)-1-tetralone 77.5 g of N-bromopropylphthalimide are added to a stirred solution of 6-hydroxy-1-tetralone (48.6 g) and potassium carbonate (39.9 g) in dimethylformamide (480 ml). The reaction mixture is stirred at RT overnight, and then poured into a stirred mixture of H2 O and methylene chloride. The layers are separated and the aqueous portion washed with methylene chloride. The combined methylene chloride fractions are washed with H2 O, dried over sodium sulfate, filtered and the filtrate evaporated in vacuo, yielding an off-white solid which is recrystallized from absolute ethanol, yielding 73.1 g of crystals, M.P. 143-145 C. | |
With potassium carbonate; In N-methyl-acetamide; dichloromethane; | Step 1 6-(3-N-Phthalimidopropoxy)-1-tetralone 77.5 g of N-bromopropylphthalimide are added to a stirred solution of 6-hydroxy-1-tetralone (48.6 g) and potassium carbonate (39.9 g) in dimethylformamide (480 ml). The reaction mixture is stirred at RT overnight, and then poured into a stirred mixture of H2 O and methylene chloride. The layers are separated and the aqueous portion washed with methylene chloride. The combined methylene chloride fractions are washed with H2 O, dried over sodium sulfate, filtered and the filtrate evaporated in vacuo, yielding an off-white solid which is recrystallized from absolute ethanol, yielding 73.1 g of crystals, M.P. 143-145 C. |
Yield | Reaction Conditions | Operation in experiment |
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With potassium carbonate; In water; acetonitrile; | EXAMPLE IX Preparation of: 6-(2-chloro-4-trifluoromethylphenoxy)tetralone A stirred mixture of 0.993 gram (0.005 mole) of 3-chloro-4-fluoro-benzotrifluoride, 0.81 gram (0.005 mole) of 6-hydroxytetralone, 1.17 gram (0.0085 mole) of potassium carbonate and 125 milliliters of acetonitrile was refluxed, under a calcium chloride drying tube for about 116 hours. The reaction mixture was then cooled, diluted with 250 milliliters of water and extracted with 250 milliliters of methylene chloride. The organic extracted was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuuo affording 0.75 gram of pale brown syrup confirmed by spectroscopic analysis as the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; | <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (52.1)(3.24 g, 20 mmol) and 4-methoxybenzyl chloride (52.2) (3.13 g, 20 mmol) were dissolved in DMF (20 mL). Cs2CO3 (7.17 g, 22mmol) was added to the mixture, and the resulting mixture was stirred overnight at ambient temperature. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with saturated brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was used without further purification for the next step. MS ESI (pos.) m/e: 283 (M+1)+. | |
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; | 6-(4-Methoxy-benzyloxy)-3,4-dihydro-2H-naphthaIen-l-one (1.1). <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (3.244 g, 20 mmol) and 4-methoxybenzyl chloride (3.132 g, 20 mmol) were dissolved in DMF (20 mL). Cs2CO3 (7.168 g, 22 mmol) was added to the mixture. The resulting mixture was stirred overnight at ambient temperature. The reaction mixture was then diluted with water (200 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with saturated brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was used without further purification in the next step. MS ESI (pos.) m/e: 283 (M+l)+. <n="91"/>A-1092-WO-PCT - 89 - |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; | Example 1 6-(benzyloxy)-3,4-dihydronaphthalene-1(2H)-one To a solution of 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one (24.3 g) in acetone (160 mL), benzyl bromide (29.4 mL) and potassium carbonate (31.1 g) were added at room temperature, followed by stirring at 40C for 3.5 hours. After filtering off the insoluble matters and concentrating the filtrate, the resultant was washed with a mixed solvent of tert-butyl methyl ether-hexane (1:4), to thereby obtain the title compound (34.5 g) having the following physical properties. TLC: Rf 0.38 (hexane:ethyl acetate = 3:1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In acetic acid; | 1. 2-Chloro-N-(2-hydroxy-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-ylmethyl)acetamide. 6-Hydroxytetralone (4.87 g, 30.0 mmol) was added to a mixture of glacial acetic acid (20 mL) and concentrated H2SO4 (20 mL) cooled to 0 C. N-Hydroxymethyl-2-chloroacetamide (3.71 g, 30.0 mmol) was added and the mixture was allowed to warm to RT. After stirring overnight, the reaction was poured into ice. An orange sludge formed and the mixture was extracted thoroughly with EtOAc. The organic layer was washed with H2O and brine, dried over MgSO4 and concentrated to give an orange foam (5.6 g). Recrystalization (EtOH/H2O) afforded the title compound as orange needles (2.46 g, 9.2 mmol, 31%). MS m/z 268/270 (M++H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | 5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethane sulfonate (7.1O g), methyl acrylate (13.0 ml), l,3-bis(diphenylphosphino)propane (0.60 g) and triethylamine (10.1 ml) were dissolved in N,N-dimethylformamide (80 ml), and the resulting mixture was stirred under argon atmosphere for 10 min. To the reaction solution, palladium acetic acid (0.27 g) was added and the reaction solution was heated at 800C for 10 hours. Water and ethyl acetate were added for the extraction. The organic layer was dried over magnesium sulfate and the solvent was removed by distillation. After the purification with silica gel chromatography, the title compound was obtained (4.1O g, 74%).IH-NMR (CDC13) δ : 2.09-2.21 (m, IH), 2.67 (t, IH), 2.98 (t, IH), 3.82(s, 3H), 6.51 (d, IH), 7.39 (s, IH), 7.46 (d, IH), 7.68 (d, IH), 8.04 (d, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With 2,6-dimethylpyridine; In dichloromethane; at 0 - 20℃; | 6-hydroxy3,4-dihydro-l(2H)-naphthalenone (10.30 g) and 2,6-lutidine (14.80 ml) were dissolved in methylene chloride (150 ml), and anhydrous trifluoromethane sulfonic acid (25 g) was added thereto at 00C. The reaction solution was stirred overnight at room temperature. Dilute hydrochloric acid was added for the extraction. The organic layer was dried over magnesium sulfate and the solvent was removed by distillation. After the purification with silica gel <n="130"/>chromatography, the title compound was obtained (17.00 g, 91%).IH-NMR (CDCB) δ : 2.12 -2.24 (m, 2H), 2.69 (t, 2H), 3.02 (t, 2H), 7.18-7.23 (m, 2H), 8.14 (d, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; | Reference Example 21; 6-Cyano-1-tetralone; Step 1: To dichloromethane solution (60 mL) comprising 6-hydroxy-1-tetralone (1.0 g, product of Aldrich Company), N-phenylbis(trifluoromethanesulfoneimide) (2.2 g, product of Tokyo Chemical Industry, Co., Ltd.) and diisopropylethylamine (1.57 mL, product of Tokyo Chemical Industry, Co., Ltd.) were added at room temperature, followed by stirring overnight. Upon the completion of stirring, the reaction solution was poured over saturated sodium bicarbonate solution and extracted with dichloromethane. The organic layer was washed with saturated brine and dried over magnesium sulfate. Thus solids were removed by filtration, the filtrate was dried under reduced pressure and obtained residues were subjected to flash column chromatography (using 10/1 (v:v) hexane/ethyl acetate as an eluent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
62% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
82% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
98% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
87% | With potassium carbonate; In acetonitrile; for 8h;Reflux; | General procedure: The starting material (1.0 mmol) was suspended in acetonitrile (20 mL) containing K2CO3 (2.0 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (1.2 mmol) and heated under reflux for 8 h. The reaction progress was monitored using silica gel TLC with Petroleum ether/EtOAc as mobile phase. Upon completion, the acetonitrile was evaporated in vacuo and the mixture was then poured into water, which was extracted with 3 x 50 mL of EtOAc, washed with brine, dried over anhydrous Na2SO4 and purified by chromatography (PE/EA, 50:1, 20:1, 10:1) on silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: 6-Hydroxy-1-tetralone (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: 6-Hydroxy-1-tetralone (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
88% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate; In acetonitrile; at 80℃; | To a solution of 6-hydroxy-1-tetralone (2.0 g, 12.3 mmol) in ACN (30 mL) was added (bromomethyl)cyclopropane (2.0 g, 14.7 mmol) and K2C03 (3.4 g, 24.6 mmol) atrt. The mixture was heated at 80 oc overnight. After the reaction was cooled to rt, it wasdiluted with EtOAc, filtered, and concentrated. The residue was purified by column chromatography (20:1 PE/EtOAc) to give 2.3 g (87%) of the title compound as a yellow solid. 1H NMR (300 MHz, CDCh): 8 0.35-0.40 (2H, m), 0.65-0.71 (2H, m), 1.25-1.32 (1H, m), 2.08-2.16 (2H, m), 2.62 (2H, t, J = 6.3 Hz), 2.93 (2H, t, J = 6.0 Hz), 3.87 (2H, d, J = 7.2 Hz), 6.71 (1H, s), 6.83 (1H, dd, J = 2.1, 8.4 Hz), 8.01 (1H, d, J = 8.4 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; | <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (3.5 g, 21.6 mmol), 3,3,3-trifluoro-1-propanol (4.93 g,43.2 mmol) and triphenylphosphine (11.3 g, 43.2 mmol) were combined in THF (80 mL). DIAD (8.7 g, 43.2 mmol) was added, and the reaction stirred overnight at rt. The solution was diluted with EtOAc (100 mL) and washed with brine. Organics were dried(MgS04) and concentrated. Purification by silica gel chromatography (10-50% EtOAc/hexanes) gave 2.93 g (53%) of the title compound as a clear oil. 1H NMR (400MHz, DMSO-d6): 8 8.02 (d, 1H, J = 8.7 Hz), 6.82 (dd, 1H, J = 8.7, 2.5 Hz), 6.71 (d, 1H, J = 2.4 Hz), 4.25 (t, 2H, J = 6.6 Hz), 2.93 (t, 2H, J = 6.1 Hz), 2.59-2.71 (m, 4H), 2.08-2.16 (m, 2H). [M+H] calc'd for C 13H 13F302, 259; found 259. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; | To a solution of6-hydroxy-3,4-dihydro-1(2H)-naphthalenone (200 mg, 1.2mmol) and 2,2,2-trifluoroethyl tosylate (345 mg, 1.4 mmol) in DMF (10 mL) was added potassium carbonate (339 mg, 2.5 mmol) at rt. The solution was heated at 100 oc overnight. The reaction was cooled, diluted with water (20 mL), and extracted withEtOAc (20 mL x 3). Organics were dried (Na2 S04) and concentrated to give 250 mg (83%) of the title compound as a yellow solid. 1H NMR (300 MHz, CDCh): 8 2.12-2.16 (2H, m), 2.64 (2H, t, J = 6.3 Hz), 2.95 (2H, t, J = 6.3 Hz), 4.34-4.46 (2H, m), 6.78 (1H,d, J = 2.4 Hz), 6.87 (1H, dd, J = 2.4, 8.7 Hz), 8.05 (1H, dd, J = 8.7 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0 - 20℃; | To a suspension of6-hydroxy-3,4-dihydro-1(2H)-naphthalenone (1.0 g, 6.0 mmol), <strong>[2566-44-1]2-cyclopropylethanol</strong> (640 mg, 7.0 mmol) and triphenylphosphine (3.25 g, 12 mmol) in THF (100 mL) was added DEAD (2.13 g, 12 mmol) at 0 C. The reaction was stirred at rt overnight. The solution was concentrated and purified by silica gel chromatography (PE:EtOAc = 12:1) to give 470 mg (33%) of the title compound as a red oil. 1H NMR (300 MHz, CDCh): 8 0.13-0.15 (2H, m), 0.50-0.52 (2H, m), 0.86-0.93 (1H, m), 1.68-1.74 (2H, m), 2.11-2.15 (2H, m), 2.64 (2H, t,J= 6.3 Hz), 2.93 (2H, t,J= 6.0Hz), 4.10 (2H, t, J = 6.6 Hz), 6.73 (1H, s), 6.83 (1H, dd, J = 2.4, 8.7 Hz), 8.02 (1H, d, J =8.7 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With potassium carbonate; In acetonitrile; at 120℃;Sealed tube; | To a solution of6-hydroxy-3,4-dihydro-1(2H)-naphthalenone (5.0 g, 30.8 mmol) and <strong>[39890-95-4]2-chloro-6-(trifluoromethyl)pyridine</strong> (5.87 g, 32.3 mmol) inACN (100 mL) was added potassium carbonate (6.39 g, 46.2 mmol), and the reaction was heated at 120oc in a sealed vessel overnight. The reaction was cooled, diluted with water (100 mL), and extracted with EtOAc (100 mL x 3). Organics were dried (Na2S04), andconcentrated. Purification by silica gel chromatography (10-80% EtOAc/hexanes) gave5.8 g (61%) of the title compound as a yellow oil. 1H NMR (400 MHz, CDCh): 8 2.13-2.20 (2H, m), 2.67 (2H, t, J= 6.2 Hz), 2.97 (2H, t, J= 6.0 Hz), 7.07-7.14 (2H, m), 7.45 (1H, d, J = 7.4 Hz), 7.89 (1H, t, J = 8.0 Hz), 8.09 (1H, d, J = 8.3 Hz). [M+H] calc'd for C16H12F3NOz, 308; found 308. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With pyridine; at 0 - 20℃; for 12h; | To a solution of 36 (900 mg, 4.4 mmol) in dry pyridine (20 mL) at 0 C was added acetic anhydride (0.63 mL, 6.6 mmol) and the reaction mixture was stirred at rt for 12 h. The reaction mixture was cooled to 0 C, quenched by adding water, extracted with ethyl acetate (350 mL). The organic part was washed with dil aq CuSO4 and work up using usual manner to obtain 37 (1.08 g, 96%) as yellow semisolid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With 1H-imidazole; In dichloromethane; at 25℃; for 19h; | Step 1): 6-((Trii sopropyl silyl)oxy)-3 ,4-dihydronaphthalen- 1 (2H)-one[00286] To a soultion of 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one (3.0 g, 18.5 mmol) and imidazole (3.15 g, 45.8 mmol) in dichloromethane (40 mL) was added triisopropylchlorosilane (4.8 mL, 98.18 mmol) dropwise slowly at 25 C, and the resulting mixture was stirred at 25 C for 19 hours. The reaction mixture was concontrated in vacuo to remove the solvent and the residue was purified by silica gel chromatography eluted with PE/EtOAc (v/v = 10/1) to give the title compound as brown oil (5.8 g, 98%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 319.3 [M+Hfb; and ‘H NMR (400 IVIHz, CDC13) (ppm): 7.94 (d, J = 8.6 Hz, 1H), 6.77 (dd, J = 8.6, 2.3 Hz, 1H), 6.68 (d, J = 2.0 Hz, 1H), 2.88 (t, J = 6.1 Hz, 2H), 2.59 (t, J = 6.3 Hz, 2H), 2.15 - 2.06 (m, 2H), 1.31 - 1.23 (m, 3H), 1.11 - 1.09 (m, 18H). |
97% | With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 3h; | Step 1: 6-((Triisopropylsilyl)oxy)-3,4-dihydronaphthalen-1(2H)-one 101g To a mixture of 6-hydroxy-3,4-dihydronaphthalen-1(2H)-one 101f (50 g, 308 mmol) and imidazole (42 g, 616 mmol) in DCM (500 mL) was added TIPSCl (71 g, 370 mmol) dropwise at 0 C. and the reaction mixture was warmed up to room temperature and the stirring continued for 3 hours. The mixture was diluted with DCM (800 mL), washed with water (400 mL*3) and two layers were separated. The organic layer was dried over Na2SO4, filtered and concentrated to afford 101g (95 g, 97% yield) as brown oil. 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J=8.4 Hz, 1H), 6.76 (dd, J=8.4, 2.0 Hz, 1H), 6.67 (d, J=2.0 Hz, 1H), 2.87 (t, J=6.0 Hz, 2H), 2.63-2.54 (m, 2H), 2.10-2.07 (m, 2H), 1.33-1.20 (m, 3H), 1.09 (d, J=7.6 Hz, 18H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.1% | General procedure: 6-Hydroxy-1-tetralone (5 g, 30.86 mmol)was placed in a 250 mL three-necked flask and dissolved in DMSO (100 mL). The flask was heated to 90 C, and K2CO3 (12.78 g) was added under stirring. Compound 4a (4.48 g, 37.03 mmol) was adde ddropwise into the flask and the reaction mixture was heated to 90 C for 4 h. The mixture was poured into water (200 mL), and the water phase was extracted twice with ethyl acetate. The organic phaseswere combined, washed with water and brine, dried with Na2SO4, and the solvent removed undervacuum to yield the crude product, which was purified by column chromatography using petroleumether/ethyl acetate (5:1) as eluent to give compound 17a as a yellow solid (75.3%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium carbonate; In dimethyl sulfoxide; at 90℃; for 2h;Cooling with ice; | To a 500 ml three-necked flask was added 16.2 g (100 mmol) of 6-hydroxy-1-tetralone, 200 ml DMSO dissolved, 41.4 g of potassium carbonate (300 mmol), Heating up 90 deg C, A solution of 13.3 g (110 mmol) of o-cyanofluorobenzene was added dropwise to the reaction, Reaction for 2 hours, The reaction solution is poured into ice water, Precipitation of light yellow solid, Filter dry, Yield 80%. In a 100 ml three-necked flask was added 40 ml of anhydrous tetrahydrofuran, Add 1.14 g of lithium aluminum hydride at room temperature for 10 minutes, To the reaction solution was slowly added 2.63 g of 2 - [(5,6,7,8 tetrahydronaphthalenone-2-yl) oxy] benzonitrile, Heating up to 65 deg C, Reflux reaction for 1 hour, Reaction finished, The mixture was added with ethanol to produce no bubbles, filter,concentrate, The product was isolated by column chromatography, Yield 73%. |
75.3% | <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (5 g, 30.86 mmol)was placed in a 250 mL three-necked flask and dissolved in DMSO (100 mL). The flask was heated to 90 C, and K2CO3 (12.78 g) was added under stirring. Compound 4a (4.48 g, 37.03 mmol) was adde ddropwise into the flask and the reaction mixture was heated to 90 C for 4 h. The mixture was poured into water (200 mL), and the water phase was extracted twice with ethyl acetate. The organic phaseswere combined, washed with water and brine, dried with Na2SO4, and the solvent removed undervacuum to yield the crude product, which was purified by column chromatography using petroleumether/ethyl acetate (5:1) as eluent to give compound 17a as a yellow solid (75.3%). IR (KBr): 2253,1688, 1597, 1577 cm-1; 1H-NMR (CDCl3), δ: 8.32-8.35 (m, 1H), 7.66-7.69 (m, 1H), 7.59-7.61 (m, 1H),7.35-7.38 (m, 3H), 7.00-7.04 (m, 1H), 2.90-2.94 (m, 2H), 2.71-2.74 (m, 2H), 2.00-2.03 (m, 2H). MS (ESI):m/z 286.34 [M + Na]+. Mp 178.3-180.5 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium carbonate; In acetonitrile; for 8h;Reflux; | General procedure: The starting material (1.0 mmol) was suspended in acetonitrile (20 mL) containing K2CO3 (2.0 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (1.2 mmol) and heated under reflux for 8 h. The reaction progress was monitored using silica gel TLC with Petroleum ether/EtOAc as mobile phase. Upon completion, the acetonitrile was evaporated in vacuo and the mixture was then poured into water, which was extracted with 3 x 50 mL of EtOAc, washed with brine, dried over anhydrous Na2SO4 and purified by chromatography (PE/EA, 50:1, 20:1, 10:1) on silica gel. |
78% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
3.5 g | With potassium carbonate; In acetone; for 4h;Reflux; | 6-Hydroxy-3,4-dihydronaphthalen-1(2H)-one(2.0 g, 12.3 mmol) and 1-(bromomethyl)-4-chlorobenzene (3.0 g, 14.8 mmol, 1.2 equivalents) were dissolved into acetone (25 mL), and potassium carbonate (3.4 g, 24.66 mmol, 2.0 equivalents) was added, followed by heating under reflux for 4 hours. Water was added to the reaction liquid, and the product was extracted with ethyl acetate. The organic layer was then washed with brine and dried over anhydrous sodium sulfate. Thereafter, the solvent was distilled off under reduced pressure to obtain a crude product. This crude product was purified through a silica gel column chromatography (eluent, ethyl acetate : hexane) to obtain 3.50 g of the title compound. 1H-NMR (400 MHz, DMSO-d6) δ: 2.06-2.15 (2H, m), 2.58-2.64 (2H, m), 2.92 (2H, t, J=6.1 Hz), 5.08 (2H, s), 6.76 (1H, d, J=2.6 Hz), 6.87 (1H, dd, J=2.6, 8.7 Hz), 7.33-7.38 (4H, m), 8.01 (1H, d, J=8.7 Hz). MS (ESI) m/z: 287 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: 6-Hydroxy-1-tetralone (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium carbonate; In acetone; for 6h;Reflux; | General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With hydroxylamine hydrochloride; sodium acetate; In water; for 1h;Reflux; | In an eggplant flask, hydroxylamine hydrochloride(7.15 g, 1.03 × 10 -1 mol), sodium acetate(14.3 g, 1.75 * 10 mol),6-hydroxyl-1-tetralone (5.00 g, 3.08 × 10 -2 mmol) and 35 ml of ion exchanged water were placed and refluxed for 1 hour with stirring.After confirming by pH test paper that the reaction solution is around pH 6,Extraction was carried out with diethyl ether. Magnesium sulfate and activated carbon were placed in this extract,After stirring for 2 hours, filtration was carried out, and the solvent was distilled off to obtain a product.The obtained product was purified by recrystallization (solvent: toluene)To obtain white crystals of the compound represented by the following formula which is the target compound.The yield was 3.25 g (yield: 60%).The analysis results of the obtained crystals are shown below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With sodium acetate; In water; at 80℃; for 2h; | Add ethoxyamino hydrochloride (1.88 g, 30.9 mmol) and sodium acetate (2.5 g, 30.9 mmol) into the solution of 6-hydroxy-1-tetralone (1 g, 6.2 mmol) in water (10 ml). Agitate the mixture solution 2 hours at 80 C. Then extract it with ethyl acetate. Dry the organic phase with anhydrous Na2SO4 before filter and evaporate to obtain the title compound (yellow solid, 0.8 g, yield of 63%). LCMS(ESI)m/z:206(M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In acetone; at 20℃; for 16h; | To a solution of 8-hydroxy-1 -tetralone (2.52 g, 15.23 mmol), in acetone (100 ml), was added potassium carbonate (2.10 g, 15.23 mmol) and pivaloyl chloride (1 .88 ml, 15.23 mmol). The reaction mixture was stirred at room temperature for 16h, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with a gradient of heptane in EtOAc (100/0 to 70/30; v/v) to give 3.75 g (100%) of 5-oxo-5,6, 7, 8-tetrahydronaphthalen-2-yl pivalate (Ia1 ). LC/MS (m/z, MH+): 247 |
100% | With potassium carbonate; In acetone; at 20℃; for 16h;Inert atmosphere; | To a solution of 8-hydroxy-1-tetralone (2.52 g, 15.23 mmol), in acetone (100 ml), was added potassium carbonate (2.10 g, 15.23 mmol) and pivaloyl chloride (1.88 ml, 15.23 mmol). The reaction mixture was stirred at room temperature for 16 h, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with a gradient of heptane in EtOAc (100/0 to 70/30; v/v) to give 3.75 g (100%) of 5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl pivalate (Ia1). LC/MS (m/z, MH+): 247 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With 2,6-dimethylpyridine; In dichloromethane; at 0℃; for 1h; | Compound 10-1 (3.70 g, 22.8 mmol) and 2.6-lutidine (12.2 mL) were dissolved in 50 mL of dichloromethane,Cooled to 0 C,Slowly adding trifluoroacetic anhydride,The reaction mixture was stirred at 0 C for 1 hour,80 mL of water was added to the system to quench the reaction,After stirring at room temperature for 15 minutes,The mixture was diluted with methylene chloride,Separate the organic layer,Sodium carbonate solution (100 mL)Washed with brine (100 mL),Dried over anhydrous sodium sulfate,Spin dry,The compound was obtained by column 10-2 (4.50 g, 67%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In N,N-dimethyl-formamide; at 120℃; for 20h;Inert atmosphere; | A mixture of 6-hydroxy-3,4-dihydronaphthalen-l(2H)-one (7.00 g, 43.16 mmol, 1 eq), iodobenzene (17.61 g, 86.32 mmol, 9.62 mL, 2 eq), Cul (822 mg, 4.32 mmol, 0.1 eq), Cs2C03 (14.06 g, 43.16 mmol, 1 eq) and Ν,Ν'-dimethyl ethane- 1,2-diamine (760 mg, 8.63 mmol, 928 uL, 0.2 eq) in DMF (20 mL) was degassed and purged with N2 3 times, and then the mixture was stirred at 120 C for 20 hr under N2 atmosphere. The reaction mixture was filtered, and the filtrate was diluted with H20 (20 mL) and extracted with EtOAc (20 mL * 2). The combined organic layers were washed with brine (30 mL * 2), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (S1O2, Petroleum ether/Ethyl acetate=50: l to 20: 1). Example 115A (2.80 g, 11.75 mmol, 27% yield) was obtained as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Compound 1 (492.7 mg, 1.23 mmol, 2.0 eq) was added to a 25 ml single-mouth flask.Compound 2 (162.2 mg, 0.62 mmol, 1.0 eq) and molecular sieves (2.0 g, 4A) were replaced by a vacuum oil pump to replace the air inside the reaction apparatus with nitrogen. Dichloromethane (4.0 ml) was added to the flask to put the apparatus. In an ice bath, stir for 10 minutes. Slowly add boron trifluoride diethyl etherate (83.7mml, 0.68mmol, 1.1eq) using a syringe. Continue stirring for 10 minutes after the addition is complete. Remove the ice bath and allow the reaction solution to warm naturally. At room temperature (20C), the progress of the reaction was checked by TLC until the starting material disappeared (2 hours); the reaction solution was slowly poured into a beaker containing a saturated solution of sodium hydrogencarbonate (20 ml) and quenched against the aqueous phase of the mixture. Extract with dichloromethane (20 ml x 3), combine the organic phases, wash with water (20 ml), wash with saturated sodium chloride (20 ml), dry over anhydrous sodium sulfate, filter the mixture, and remove the solvent on a rotary evaporator. The crude product was purified on a silica gel column eluting with ethyl acetate/petroleum ether = 40% to give a white solid.242 mg, yield: 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With pyridinium p-toluenesulfonate; In dichloromethane; at 10℃; | Step 1: Preparation 6-tert-butoxytetralin-1-one To a stirred solution of 6-hydroxytetralin-1-one (50 g, 308.29 mmol, 1 eq) in anhydrous dichloromethane (2000 mL) at 0 C. was added tert-butyl 2,2,2-trichloroethanimidate (67.36 g, 308.29 mmol, 55 mL, 1 eq) and pyridinium para-toluenesulfonate (7.75 g, 30.83 mmol, 0.1 eq). The reaction mixture was stirred at 10 C. for 3 hours. Additional portion of tert-butyl 2,2,2-trichloroethanimidate (67.36 g, 308.29 mmol, 55 mL, 1 eq) and pyridinium para-toluenesulfonate (7.75 g, 30.83 mmol, 0.1 eq) was added and the reaction mixture was stirred at 10 C. for 15 hours. This process was repeated three times. Thin layer chromatography (petroleum ether:ethyl acetate=3:1, Rf=0.8) showed that most of reactant still remained, the reaction mixture was stirred at 10 C. for 72 hours. The reaction mixture was quenched by addition of a solution of sodium hydrogen carbonate (1500 mL) at 15 C., and then extracted with dichloromethane (300 mL*3). The combined organic layers were washed with brine (300 mL*2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=100:1 to 50:1) to get 6-tert-butoxytetralin-1-one (21 g, 96.20 mmol, 31% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J=8.8 Hz, 1H), 6.91 (dd, J=2.4, 8.8 Hz, 1H), 6.82 (d, J=2.0 Hz, 1H), 2.93-3.90 (t, J=6.0 Hz, 2H), 2.63-2.60 (m, t, J=6.0 Hz, 2H), 2.13 (m, 2H), 1.43 (s, 9H) |
31% | To a stirred solution of 6-hydroxytetralin-1-one (50 g, 308.29 mmol, 1 eq) in anhydrous dichloromethane (2000 mL) at 0 C. was added tert-butyl 2,2,2-trichloroethanimidate (67.36 g, 308.29 mmol, 55 mL, 1 eq) and pyridinium para-toluenesulfonate (7.75 g, 30.83 mmol, 0.1 eq). The reaction mixture was stirred at 10 C. for 3 hours. Additional portion of tert-butyl 2,2,2-trichloroethanimidate (67.36 g, 308.29 mmol, 55 mL, 1 eq) and pyridinium para-toluenesulfonate (7.75 g, 30.83 mmol, 0.1 eq) was added and the reaction mixture was stirred at 10 C. for 15 hours. This process was repeated three times. Thin layer chromatography (petroleum ether:ethyl acetate=3:1, Rf=0.8) showed the most of reactant was still remained, the reaction mixture was stirred at 10 C. for 72 hours. The reaction mixture was quenched by addition a solution of sodium hydrogen carbonate (1500 mL) at 15 C., and then extracted with dichloromethane (300 mL*3). The combined organic layers were washed with brine (300 mL*2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=100:1 to 50:1) to get 6-tert-butoxytetralin-1-one (21 g, 96.20 mmol, 31% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J=8.8 Hz, 1H), 6.91 (dd, J=2.4, 8.8 Hz, 1H), 6.82 (d, J=2.0 Hz, 1H), 2.93-3.90 (t, J=6.0 Hz, 2H), 2.63-2.60 (m, t, J=6.0 Hz, 2H), 2.13 (m, 2H), 1.43 (s, 9H) | |
31% | To a stirred solution of 6-hydroxytetralin-l-one (50 g, 308.29 mmol, 1 eq) in anhydrous dichloromethane (2000 mL) at 0 C. was added tert-butyl 2,2,2-trichloroethanimidate (67.36 g, 308.29 mmol, 55 mL, 1 eq) and pyridinium para-toluenesulfonate (7.75 g, 30.83 mmol, 0.1 eq). The reaction mixture was stirred at 10 C. for 3 hours. Additional portion of tert-butyl 2,2,2-trichloroethanimidate (67.36 g, 308.29 mmol, 55 mL, 1 eq) and pyridinium para-toluenesulfonate (7.75 g, 30.83 mmol, 0.1 eq) was added and the reaction mixture was stirred at 10 C. for 15 hours. This process was repeated three times. Thin layer chromatography (petroleum ether: ethyl acetate=3:1, Rf=0.8) showed that most of reactant still remained, the reaction mixture was stirred at 10 C. for 72 hours. The reaction mixture was quenched by addition of a solution of sodium hydrogen carbonate (1500 mL) at 15 C., and then extracted with dichloromethane (300 mL×3). The combined organic layers were washed with brine (300 mL×2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate=100:1 to 50:1) to get 6-tert-butoxytetralin-l-one (21 g, 96.20 mmol, 31% yield) as a yellow oil. 1H NMR (400 Mhz, CDCl3) δ 7.97 (d, J=8.8 Hz, 1H), 6.91 (dd, J=2.4, 8.8 Hz, 1H), 6.82 (d, J=2.0 Hz, 1H), 2.93-3.90 (t, J=6.0 Hz, 2H), 2.63-2.60 (m, t, J=6.0 Hz, 2H), 2.13 (m, 2H), 1.43 (s, 9H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With perchloric acid; acetic acid; for 1.5h;Reflux; | In a 100mL round bottom flask, mix 4-diethylaminosalicyaldehyde (1.93g, 10mmol), 6-hydroxy-1-tetralone (1.62g, 10mmol) and perchloric acid (3mL) Dissolve in acetic acid (20 mL) and reflux the mixture for 1.5 hours. After cooling to room temperature, the solution was poured into a mixture of ethyl acetate (15 mL) and petroleum ether (15 mL). The precipitate was filtered and washed with ethanol, and then dried under vacuum to obtain pure dark purple solid compound 1 (2.88 g, yield: 90%). |
68% | With sulfuric acid; at 0 - 90℃; for 7h; | First, 6-hydroxy-1-tetralone (0.6 g, 2.7 mmol) was slowly added intoconcentrated H2SO4 (1.85 mL), followed by cooling to 0 C. Second, 4-(diethylamino)salicylaldehyde (0.784 g, 4.06 mmol) was added in portionsover 1 h under vigorous stirring. Next, the reaction mixture washeated to 90 C for 6 h. The resulting mixture was poured into ice (40 g)after cooling to room temperature. The mixture was stirred for 20 min,followed by extraction using CH2Cl2/CH3OH (7×20 mL, v/v 10:1).The crude product was purified by silica-gel column chromatographyusing CH2Cl2/CH3OH as the eluent, affording the final product in 68%yield (0.588 g). 1H NMR (300 Hz, DMSO-d6): δ 8.42 (2H, s), 8.10 (2H,d), 7.81 (2H, d), 7.29 (2H, m), 7.18 (2H, s), 6.81 (2H, m), 6.72 (2H, d),3.63 (8H, q), 2.96 (8H, s), 1.22 (13H, t). 13C NMR (75 MHz, DMSO-d6) δ164.27, 157.71, 154.77, 147.80, 145.68, 131.49, 128.88, 120.17,117.45, 117.15, 115.66, 45.21, 26.48, 24.61, 12.37. MS (ESI, m/z)Calcd for [C21H22NO2]+: 320.1645, found: 320.1960. |
63% | With sulfuric acid; acetic acid; at 20℃; for 12h; | A solution of 6-hydroxy-1-tetralone (0.16 g, 0.99 mmol) with one equivalent of 4-(diehylamino) salicylaldehyde (0.2 g, 1mmol) in a mixture of concentrated sulfuric acid/glacial acetic acid (4 mL:1mL) was violentlystirred for 12 h at room temperature. Then ethyl acetate was added to the mixture solution and gradually formed a precipitate. The obtained dark-yellow solid was filtered and washed with diethyl ether for several times, the residue was dried under vacuum to give the product HDA-H (0.2 g, yield = 63%). 1H NMR (600 MHz, DMSO) δ 8.63 (s,1H), 8.16 (d, J = 8.7 Hz, 1H), 7.93 (t, J = 14.5 Hz, 1H), 7.41 (dd, J =9.3, 2.4 Hz, 1H), 7.26 (t, J = 10.0 Hz, 1H), 6.95 (dd, J = 8.7, 2.4 Hz,1H), 6.87 (d, J = 2.3 Hz, 1H), 3.74-3.63 (m, 4H), 3.08-2.96 (m, 4H),1.24 (t, J = 7.1 Hz, 6H) (Fig. S6). 13C NMR (151 MHz, DMSO) δ 164.76,164.32, 158.25, 155.24, 148.39, 146.22, 132.06, 129.43, 120.71, 117.67,116.18, 96.14, 45.71, 26.99, 25.11, 12.88 (Fig. S7). ESI-MS:320.1644(M+), cald for C21H22NO2+ 320.1645 (Fig. S8). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 16h; | Compound (III-1) (300 mg, 1.56 mmol), compound (II-46) (279 mg, 1.72 mmol), tris(dibenzylideneacetone)dipalladium(143 mg, 0.156 mmol), xantphos (271 mg, 0.468 mmol) and cesium carbonate (1.52 g, 4.68 mmol) weredissolved in 1,4-dioxane (5.0 mL), and the mixture was stirred at 90C for 16 hr. The reaction mixture was filtered, andthe filtrate was diluted with ethyl acetate, and washed successively with saturated aqueous sodium hydrogen carbonatesolution and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and filtered, and the solventwas evaporated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethylacetate) to give compound (IV-68) (yield 222 mg, 52%) as a pale-yellow white solid |
52% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 16h; | Compound (III-1) (300 mg, 1.56 mmol),Compound (II-46) (279 mg, 1.72 mmol),Tris (dibenzylideneacetone) dipalladium (143 mg, 0.156 mmol),Xantphos (271 mg, 0.468 mmol)And cesium carbonate (1.52 g, 4.68 mmol)Was dissolved in 1,4-dioxane (5.0 mL)Followed by stirring at 90 C. for 16 hours. After filtering the reaction solution,The filtrate was diluted with ethyl acetate,And successively washed with a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution.The organic layer was dried over anhydrous sodium sulfate,After filtration, the solvent was distilled off under reduced pressure.The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate)Compound (IV-68)(Yield 222 mg, Yield 52%)As a pale yellowish white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.00 parts of a salt represented by the formula (I-1-a) and 35 parts of chloroform were mixed and stirred at 23 C. for 30 minutes. To the resulting mixture, 2.85 parts of the compound represented by the formula (I-1-b) was added, followed by stirring at 50 C. for 2 hours. After cooling the resulting mixture to 23 C.,2.85 parts of the compound represented by the formula (I-2-d), and the mixture was further stirred at 23 C. for 18 hours. 100 parts of chloroform and 50 parts of ion exchanged water were added to the obtained mixture, and the mixture was stirred at 23 C. for 30 minutes, then separated, and the organic layer was taken out. To the obtained organic layer, 5% aqueous oxalic acid solution, And the mixture was stirred at 23 C. for 30 minutes, then separated, and the organic layer was taken out. 50 parts of ion-exchanged water was added to the obtained organic layer, and the mixture was stirred at 23 C. for 30 minutes, then separated, and the organic layer was taken out. This washing operation was repeated 5 times. After filtering the obtained organic layer, the filtrate was concentrated30 parts of tert-butyl methyl ether was added to the concentrated residue, and the mixture was stirred at 23 C. for 30 minutes, then the supernatant liquid was removed and concentrated to obtain a salt represented by the formula (I-2-e) 5.65 parts was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 80℃; for 16h; | 6-Hydroxy-1-tetralone (39) (1.0 g, 6.16 mmol) was suspended in DMF (15 mL)containing K2C03 (2.0 g, 14.46 mmol) and KI (0.5 g). The reaction solution was treated with 4-fluorophenethybromide (48) (1.5 g, 7.38 mmol) and heated under 80C for 16 hours. Thereaction progress was monitored using silica gel TLC with ethyl acetate:hexane (1:3). Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by column chromatography (ethyl acetate/hexane, 1:4) to give Compound 49 (1.2g. 68 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With hydrogenchloride; In methanol; water; at 60 - 80℃; for 6h; | General procedure: To a solution of (7) 1-(<strong>[4649-09-6]1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde</strong> (0.300g, 2.053mmol) in 32% aqueous HCl/methanol (1.5:1 v/v) (4.5ml/3 ml) was added a selected bicyclic scaffold (tetralone, indanone, 3-coumaranone, 4-chromanone and thiochroman-4-one) (2.053mmol) and the reaction was refluxed for at least 6h at 60-80C. The progress of the reaction was monitored by silica gel TLC with ethyl acetate as mobile phase. When the reaction reached completion, the target products were isolated by precipitation with ice-cold water, after which they were purified by recrystallisation with ethanol. |
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Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
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P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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