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CAS No. : | 6272-38-4 | MDL No. : | MFCD00002186 |
Formula : | C13H12O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CCZCXFHJMKINPE-UHFFFAOYSA-N |
M.W : | 200.23 | Pubchem ID : | 80459 |
Synonyms : |
|
Num. heavy atoms : | 15 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.08 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 59.44 |
TPSA : | 29.46 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | Yes |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.57 cm/s |
Log Po/w (iLOGP) : | 2.45 |
Log Po/w (XLOGP3) : | 2.75 |
Log Po/w (WLOGP) : | 2.82 |
Log Po/w (MLOGP) : | 2.69 |
Log Po/w (SILICOS-IT) : | 2.92 |
Consensus Log Po/w : | 2.72 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.21 |
Solubility : | 0.124 mg/ml ; 0.00062 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.02 |
Solubility : | 0.19 mg/ml ; 0.000947 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.49 |
Solubility : | 0.00649 mg/ml ; 0.0000324 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.54 |
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 |
---|---|---|
56% | With potassium hydroxide In N,N-dimethyl-formamide at 80 - 90℃; | |
44% | With potassium hydroxide In methanol at 20℃; Reflux; | |
43% | With potassium hydroxide In methanol at 20℃; for 5.16h; Inert atmosphere; Reflux; |
37% | With sodium methylate In methanol for 2h; Heating; | |
32% | Stage #1: benzene-1,2-diol With sodium hydroxide In methanol at 0 - 3℃; Stage #2: benzyl chloride In methanol for 2h; Heating; | |
12.5% | With potassium carbonate; potassium iodide In acetone at 50℃; chemoselective reaction; | |
With potassium carbonate | ||
With xylene | ||
With potassium hydroxide | ||
With sodium ethanolate | ||
With potassium hydroxide In N,N-dimethyl-formamide | ||
With potassium carbonate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In tetrahydrofuran; water at 20℃; for 20h; | |
62.5% | Stage #1: O-benzylcatechol With sodium hydroxide In 1,4-dioxane; water at 45℃; Stage #2: epichlorohydrin In 1,4-dioxane; water at 45℃; | |
With potassium hydroxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium carbonate for 10 - 12h; Heating / reflux; | 8 A mixture of phenol derivative 85 (1 equiv.), α,ω-dibromoalkane (1.5 equiv.) and anhydrous potassium carbonate was stirred under refluxed in dry acetone or acetonitrile for 10-12 hours, then it was cooled to room temperature and solid materials were filtered off. The filtrate was evaporated, water was added to the residue and the mixture was extracted with diethyl ether. The ethereal layer was washed with 10% sodium hydroxide solution, water and brine, dried (MgSO4) and concentrated under reduced pressure. Purification by flash column chromatography on silica gel (diethyl ether-hexane) gave compound 86 as colorless viscous oil in 68-74% yields. |
With potassium hydroxide In methanol for 8h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With sodium hydroxide In dimethyl sulfoxide at 75℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 2h; | 1 Synthesis of l-(benzyloxy)-2-d3-methoxybenzene (19). Iodomethane-d3 (25 g, 172 mmol) was added to a solution of 2-(benzyloxy)phenol (25 g, 125 mmol) in 500 mL DMF followed by potassium carbonate (19 g, 137 mmol). The mixture was stirred at 80 °C for 2 h. The solid was removed by filtration and washed with ethyl acetate (200 mL). The organic filtrate was washed sequentially with saturated sodium bicarbonate and brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give a yellow solid. The crude product was purified by chromatography on silica gel (20 % ethyl acetate/heptanes) to give 27.8 g (102%) of 19 as a white solid. |
94% | With caesium carbonate In N,N-dimethyl-formamide for 2h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With sodium hydroxide In dimethyl sulfoxide at 75℃; for 1h; | |
45% | Stage #1: O-benzylcatechol With potassium carbonate In acetone Inert atmosphere; Reflux; Stage #2: diethylene glycol dimesylate In acetone for 20h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium hydride In N,N-dimethyl-formamide at 70℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium carbonate In acetone for 24h; Heating; | |
58.4 g (84%) | With sodium hydroxide; potassium carbonate In diethyl ether; water | 132 3-(2-Benzyloxyphenoxy)propyl chloride PREPARATION 132 3-(2-Benzyloxyphenoxy)propyl chloride A mixture of 50 g (0.25 mole) of 2-benzyloxyphenol, 78.7 g (0.5 mole) of 1-bromo-3-chloropropane and 103.7 g of anhydrous potassium carbonate in 1 liter of actone was heated at reflux for 24 hr. The reaction mixture was cooled, filtered and concentrated in vacuo to give 67.2 g of a tan oil as residue. The oil was dissolved in 300 ml of ethyl ether and washed with 100 ml of a 5% sodium hydroxide solution. A solid precipitated, about 200 ml of water was added and the precipitated sold redissolved. Solvent layers were separated and the ethyl ether layer washed twice with a 5% sodium hydroxide solution. The organic layer was next washed with water, brine, and dried over sodium sulfate and concentrated to give 58.4 g (84%) of oil as product. |
58.4 g (84%) | With sodium hydroxide; potassium carbonate In diethyl ether; water; acetone | 146 1-Chloro-3-[(2-phenylmethoxy)phenoxy]propane PREPARATION 146 1-Chloro-3-[(2-phenylmethoxy)phenoxy]propane A mixture of 50g (0.25 mole) of 2-benzyloxyphenol, 78.7 g (0.5 mole) of 1-bromo-3-chloropropane and 103.7 g (0.75 mole) of anhydrous potassium carbonate in one liter of acetone was heated at reflux for ~24 hr. The mixture was worked up to give 67.2 g of tan oil as residue. The oil was dissolved in ~300 ml of ethyl ether and washed with 100 ml of 5% sodium hydroxide solution and a solid precipitated. Approximately 200 ml of water was added and the solid dissolved. The layers were then separated. This process was repeated twice with 100 ml of 5% sodium hydroxide solution. The organic layer was washed with water and brine, dried over sodium carbonate, and concentrated to give 58.4 g (84%) of oil as residue. NMR was consistent for the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 48h; Inert atmosphere; | |
With potassium hydroxide In ethanol for 6h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium hydroxide In dimethyl sulfoxide at 75℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.4% | With potassium dihydrogenphosphate; potassium nitrososulfonate In water; acetone at 4 - 20℃; for 3h; | 3.1 To an eggplant type flask (100 mL), 2-(benzyloxy)phenol (200.2 mg, 1.0 mmol, 1.0 equivalent) and acetone (5 mL) were added. To this stirred solution, distilled water (15 mL) containing KH2PO4 (204 mg, 1.5 mmol, 1.5 equivalents) was added. A Fremy salt (i.e., potassium nitrososulfonate; 1.07 g, 4.0 mmol, 4.0 equivalents) was dissolved in distilled water (40 mL) cooled to 4 DEG C and containing KH2PO4 (544 mg, 4.0 mmol, 4.0 equivalents), and the solution was quickly added dropwise at room temperature. After the dropping was completed, the mixture was stirred at room temperature for 3 hours, and then the solution color was changed to dark brown and a yellow precipitate was formed. It was observed that the starting materials were almost dissolved at this stage. [0114] After the reaction was completed, ethyl acetate (40 mLx1, 20 mLx1) was added, and an aqueous layer was extracted. The resulting organic layer was washed with saturated brine (10 mLx1), dried over sodium sulfate (5 g), and concentrated under a reduced pressure to obtain crude solid crystals (224.3 mg). The crude crystals were purified by silica gel chromatography [21.7 (diameter) x7.5 cm, 6 g; n-hexane:ethyl acetate (6:1)] to obtain 2-benzyloxy-1,4-benzoquinone (182.9 mg, yield = 83.4%) as pale brown crystals.TLC: Rf = 0.41 (n-hexane/ethyl acetate = 2:1<1>H-NMR (CDCl3, delta ppm): 5.05 (s, 2H, CH2Ph), 6.00 (s, 1H, H-3), 6.71 (s, 2H, H-5, 6), 7.40 (s, 5H, Ph-)IR (KBr cm): 3080, 2344, 1674, 1642, 1596, 1504, 1454, 1386, 1360, 1316, 1248, 1210, 1112, 1004, 886, 836, 728, 692, 466, 424 |
82% | With potassiuim nitrosodisulfonate | |
82% | With potassium dihydrogenphosphate; potassiuim nitrosodisulfonate In water; acetone at 20℃; |
42.4% | Stage #1: O-benzylcatechol In acetonitrile at 20℃; Stage #2: With oxygen In acetonitrile at 20℃; for 24h; | 3.2 To an eggplant type flask (100 mL), 2-benzyloxyphenol (206 mg, 1.03 mmol, 1.0 equivalent) and acetonitrile (20 mL) were added. To this stirred solution, Co(bpb)H2O (38.5 mg, 0.098 mmol, 0.05 equivalent) was added at room temperature. The mixture color was changed from brownish green to brown. In this connection, Co(bpb)H2O is aqua-[N,N-bis((2'-pyridine-carboxamido)-1,2-benzene]cobalt (II). Oxygen was blown into the reaction mixture at the flow rate of 100 mL/min for 24 hours in total, but the starting materials still remained. After the reaction was completed, the solvent was concentrated under a reduced pressure and evaporated. The resulting residue was purified by silica gel chromatography [2.5(diameter)*4.0 cm, 10 g; n-hexane:ethyl acetate (10:1)] to obtain 2-benzyloxy-1,4-benzoquinone (93.5 mg, yield = 42.4%) in Fraction Nos. 11-16 as golden crystals, and further obtain the starting material (114.7 mg, 55.6%) in Fraction Nos. 2-4 as colorless oil. This yield corresponds to 95.5% in view of the recovery of the starting material. TLC: Rf = 0.41 (n-hexane/ethyl acetate = 2:1) |
With potassiuim nitrosodisulfonate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.9% | With sodium hypochlorite; sodium iodide; sodium hydroxide In methanol at -10 - 10℃; for 0.166667h; | 6.1 Stej 1[0337] A solution of 2-(benzyloxy)phenol (63.7 ml, 364 mmol) in MeOH (1050 ml) was cooled to -10 °C and sodium iodide (54.5 g, 364 mmol) and sodium hydroxide (382 ml, 764 mmol) were added (NaOH over 5 mm, temp to 10 °C and dark solution with NaOH addition). Cooled back to <5 °C and added sodium hypochlorite (247 ml, 400 mmol) dropwise, keeping the temperature at < 5 °C.After 10 mm, removed 500 mL MeOH by rotary evaporation, then added MTBE (730 mL) and 2 N HCI (909 ml, 1818 mmol), washed with 1 N Na2S2O3 (130 mL x 3; lighter each time) and brine (64 mL), dried (Na2SO4), conc, and flushed with cyclohexane (100 mL) to a crude yellow solid. Added cyclohexane (130 mL), heated to 55 °C (yellow solution), then cooled slowly, seeding at 45 °C ( 50 mg-15 solution) and 40 °C ( 50 mg, slurry developed). Continued cooling to roomtemperature (‘‘20-252C) and stirred vigorously overnight. Filtered, washing with cyclohexane (64 mL), giving crop 1 material (69.93 g, 59%, very pure by 1 H NMR, slightly off-white solid). Concentrated the mother liquors to 70 mL, seeded, aged 1 h, and sticky dark material was precipitating with product. Added MTBE (7 mL),sonicated (good for color dissolution), stirred 20 mm, and filtered. Washed with10% MTBE/cyclohexane (32 mL), giving crop 2 material (4.65 g, some small impurities by 1 H NMR). Overall, isolated 2-(benzyloxy)-4-iodophenol (74.6 g, 229 mmol, 62.9 % yield). 1H NMR (501 MHz, DMSO-d6) 6 9.33 (5, 1 H), 7.49 -7.42 (m, 2H), 7.42 - 7.35 (m, 2H), 7.35 - 7.29 (m, 1 H), 7.24 (d, J = 2.0 Hz, 1 H), 7.09(dd, J = 8.3, 2.1 Hz, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 5.09 (5, 2H). |
58% | With Iodine monochloride In diethyl ether | |
35% | Stage #1: O-benzylcatechol With sodium hydroxide; sodium iodide In methanol Stage #2: With sodium hypochlorite at 0 - 2℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium hydroxide In 1,4-dioxane at 80℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sodium hydroxide In 1,4-dioxane at 80℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With bromine; acetic acid In dichloromethane at 0℃; for 0.333333h; Inert atmosphere; | |
78% | With bromine; acetic acid In dichloromethane at 20℃; | |
77% | With bromine In dichloromethane; acetic acid at 0℃; for 0.333333h; |
55% | With bromine; acetic acid at 0℃; for 1h; | |
52% | With bromine; acetic acid In dichloromethane at 0℃; for 0.333333h; | 7.1 Step 1: 2-benzyloxy-4-bromophenol Add 2-(benzyloxy)phenol (5.0 g, 25 mmol), dichloromethane (40 mL), and acetic acid (20 mL) to the reaction flask, and cool to 0°C.Dissolve bromine (1.3mL, 25mmol) in acetic acid (15ml), slowly add dropwise to the above solution, and continue stirring for 20 minutes after the drop.After the completion of the reaction detected by TLC, the reaction solution was washed with saturated sodium sulfite solution (50mL) and saturated sodium chloride (50mL), and the solvent was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (PE/EA(V/V)=10/ 1) Purification,The title compound was obtained as a colorless oily product (3.6 g, 13 mmol, 52%). |
With N-Bromosuccinimide In acetonitrile at 20℃; for 5h; | 351.a 2-Benzyloxy-4-bromophenol [310.1] 12 g of 2-Benzyloxyphenol was dissolved in 300 ml of acetonitrile, 10.7 g of N-bromosuccinimide was added thereto, and the mixture was stirred at room temperature for 2 hours. Additional N-bromosuccinimide (1 g) was added thereto and the mixture was stirred for 1 hour, and further additional N-bromosuccinimide (1 g) was added thereto and the mixture was stirred for 2 hours. The reaction mixture was concentrated, and the residue was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate and then filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography, to give 14.927 g of the title compound in the 10:1 hexane-ethyl acetate fraction.1H-NMR(CDCl3) δ: 5.08 (s, 2H) 5.60 (s, 1H) 6.82 (d, J=8.0Hz, 1H) 7.01 (dd, J=2.4, 8.4Hz, 1H) 7.06 (d, J=2.4Hz, 1H) 7.36-7.42 (m, 5H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate In N,N-dimethyl-formamide at 90℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In dichloromethane at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | Stage #1: O-benzylcatechol With sodium hydride In N,N-dimethyl-formamide at 20℃; for 1.5h; Stage #2: chloroacetaldehyde dimethyl acetal In N,N-dimethyl-formamide at 120℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With di-isopropyl azodicarboxylate; triphenylphosphine In 1,2-dimethoxyethane at 20 - 50℃; for 24h; | 25 To a stirring mixture at room temperature of (S)-3-hydroxymethyl-piperidine-1- carboxylic acid, tert-butyl ester (2.65 g, 12.31 mmol), 2-(benzyloxy)-phenol (2.4 mL, 13.70 mmol), and triphenylphosphine (4.04 g, 15.40 mmol) in 20 mL of 1 ,2- dimethoxyethane was added drop wise diisopropyl azodicarboxylate (3.1 mL, 15.74 mmol). Addition was exothermic, after which all solid was in solution. The solution was heated at 50 0C under N2 for 24 hours, rotary evaporated (to remove most of the 1 ,2- dimethoxyethane), then suspended into 75 mL of hexanes. The solid that formed was removed by filtration. The filtrate was rotary evaporated and chromatographed (MPLC, silica gel, 100% CH2CI2 [2L] then 20% EtOAc in hexanes [2L]) to give 3.96 g (81 %) of (S)- 3-(2-benzyloxy-phenoxymethyl)-piperidine-1-carboxylic acid terf-butyl ester as light yellow oil. MS (APCI+) m/z 298.2 [M-99, 100%]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In ethanol at 25℃; for 25.5h; Heating / reflux; | 1a; 1b The free acid of was prepared by preparing a solution of 27.5 ml (31.4 g, 157 mmol) of 2-benzyloxyphenol, 80.0 ml (118.82 g, 434 mmol) of 1,8-dibromooctane and 100' ml of ethanol was treated with 23.18 g (168 mmol) of potassium carbonate and heated to reflux for 5.5 hours. The cooled reaction mixture was stirred for 20 hours at 25 °C, filtered and concentrated. The residue was diluted with 100 ml of 2:1 hexanes/ethyl acetate and decolorized with charcoal. The solution was concentrated. This residue was purified by Kugelrohr distillation to remove the excess dibromide at 98° C and 0.5 mm of pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate In acetone at 95 - 110℃; for 44h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate In acetone at 85 - 120℃; for 67h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate In acetone for 3h; Reflux; | |
90% | With choline chloride; urea; potassium hydroxide at 80℃; for 2h; Green chemistry; | Representative reaction condition General procedure: Phenol (0.5 mmol), benzyl bromide(1.2 mmol) and KOH (2.0 mmol) was added to the DES (1 mL) and heated at temperature (80°C) for 2 h. After cooling to room temperature water was added and the product was extracted with ethyl acetate (1 3 mL) andanalyzed by GC-MS after the addition of hexamethylbenzene as an internal standard. The product was purified using column chromatography on silica gel(hexane/EtOAc::99:1). The pure product was characterized by 1H NMR and 13CNMR.Table 4 Comparison of different methodologies for benzylation of phenols with benzyl bromide |
90% | With potassium carbonate In acetone at 56℃; for 3h; |
59% | With potassium carbonate In N,N-dimethyl-formamide for 3h; | A A. 2-(Benzyloxy)phenol To a stirred solution of pyrocatechol (3.00 g, 27.2 mmol) in DMF (30 mL) was added potassium carbonate (4.14 g, 30.0 mmol) and benzyl bromide (3.89 mL, 32.7 mmol). After 3 h, the reaction mixture was quenched with water and extracted with EtOAc (3X). The combined organic layers were washed with brine, dried over Na2SC>4 and evaporated. The residue was purified on silica gel, eluting with a 0%-30% EtOAc in hexanes gradient to give the title compound (3.56 g, 59%). 1H NMR (400 MHz, CD3SOCD3) δ 5.07 (s, 2 H), 6.64-6.88 (m, 3 H), 6.94 (dd, J = 8, 1 Hz, 1 H), 7.19-7.41 (m, 3 H), 7.45 (d, J = 7 Hz, 2 H), 8.97 (s, 1 H); LC-MS (LC-ES) M+H = 201 . |
28% | With sodium hydroxide In methanol at 100℃; for 22h; | |
With potassium carbonate In acetone at 20℃; | 74 To a solution of benzene-1,2-diol (2.2g, 20mmol) and potassium carbonate (3.0g, 22mol) in acetone (50mL) was added benzyl bromine(3.42g, 2.4ml), 20mmol). The reaction was stirred at room temperature overnight, filtered and evaporated by a rotatory evaporator to obtain a colorless oil. 1HNMR (300MHz, CDCl3): δ 5.11 (s, 2H), 6.50 (m, 1H), 6.95 (m, 3H), 7.40 (m, 5H). | |
With potassium carbonate In acetone for 8h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 89.6 percent / K2CO3; (n-Bu)4NI / 7 °C / Heating 3.1: 65 percent / Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 5 h / Heating 4.1: 79 percent / cyclohexene / Pd(OH)2/C / methanol / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 73 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 59 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 45 percent / cyclohexene / Pd(OH)2/C / methanol / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 60 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 65.5 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 68 percent / cyclohexene / Pd(OH)2/C / methanol / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 89.6 percent / K2CO3; (n-Bu)4NI / 7 °C / Heating 3.1: 65 percent / Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 5 h / Heating 4.1: 79 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 5.1: 83.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 89.6 percent / K2CO3; (n-Bu)4NI / 7 °C / Heating 3.1: 65 percent / Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 5 h / Heating 4.1: 79 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 5.1: 83.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 6.1: 25 percent / aq. NaOH / 16 h / Heating 7.1: 39 percent / aq. HCl / diethyl ether / 4 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 60 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 65.5 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 68 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 41 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 25.5 percent / aq. NaOH / 16 h / Heating 9.1: 37 percent / aq. HCl / diethyl ether / 4 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 73 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 59 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 45 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 78.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 71 percent / aq. NaOH / 16 h / Heating 9.1: 60 percent / aq. HCl / diethyl ether / 4 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 60 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 65.5 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 68 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 41 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 73 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 59 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 45 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 78.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 89.6 percent / K2CO3; (n-Bu)4NI / 7 °C / Heating 3.1: 65 percent / Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 5 h / Heating 4.1: 79 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 5.1: 79 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 6.1: 25 percent / aq. NaOH / 16 h / Heating 7.1: 51 percent / aq. HCl / diethyl ether / 4 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 89.6 percent / K2CO3; (n-Bu)4NI / 7 °C / Heating 3.1: 65 percent / Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 5 h / Heating 4.1: 79 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 5.1: 79 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 73 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 59 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 45 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 82 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 60 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 65.5 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 68 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 87 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 60 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 65.5 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 68 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 87 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 90 percent / aq. NaOH / 16 h / Heating 9.1: 57 percent / aq. HCl / diethyl ether / 4 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 73 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 59 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 45 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 82 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 64 percent / aq. NaOH / 16 h / Heating 9.1: 68 percent / aq. HCl / diethyl ether / 4 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 73 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 59 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 45 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 96.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 60 percent / aq. NaOH / 16 h / Heating 9.1: 74 percent / aq. HCl / diethyl ether / 4 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 60 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 65.5 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 68 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 88 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 67.5 percent / aq. NaOH / 16 h / Heating 9.1: 56 percent / aq. HCl / diethyl ether / 4 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 60 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 65.5 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 68 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 88 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 73 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 59 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 45 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 96.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 89.6 percent / K2CO3; (n-Bu)4NI / 7 °C / Heating 3.1: 65 percent / Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 5 h / Heating 4.1: 79 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 5.1: 83.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 6.1: 25 percent / aq. NaOH / 16 h / Heating 7.1: 39 percent / aq. HCl / diethyl ether / 4 h 8.1: DCC / tetrahydrofuran / 0 - 20 °C 8.2: tetrahydrofuran / 24 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 89.6 percent / K2CO3; (n-Bu)4NI / 7 °C / Heating 3.1: 65 percent / Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 5 h / Heating 4.1: 79 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 5.1: 83.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 6.1: 25 percent / aq. NaOH / 16 h / Heating 7.1: 39 percent / aq. HCl / diethyl ether / 4 h 8.1: DCC / tetrahydrofuran / 0 - 20 °C 8.2: tetrahydrofuran / 24 h / 20 °C 9.1: 0.11 g / tetrahydrofuran / 24 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 60 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 65.5 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 68 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 41 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 25.5 percent / aq. NaOH / 16 h / Heating 9.1: 37 percent / aq. HCl / diethyl ether / 4 h 10.1: DCC / tetrahydrofuran / 0 - 20 °C 10.2: tetrahydrofuran / 24 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 89.6 percent / K2CO3; (n-Bu)4NI / 7 °C / Heating 3.1: 65 percent / Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 5 h / Heating 4.1: 79 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 5.1: 79 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 6.1: 25 percent / aq. NaOH / 16 h / Heating 7.1: 51 percent / aq. HCl / diethyl ether / 4 h 8.1: DCC / tetrahydrofuran / 0 - 20 °C 8.2: tetrahydrofuran / 24 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 73 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 59 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 45 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 78.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 71 percent / aq. NaOH / 16 h / Heating 9.1: 60 percent / aq. HCl / diethyl ether / 4 h 10.1: DCC / tetrahydrofuran / 0 - 20 °C 10.2: tetrahydrofuran / 24 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 11 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 60 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 65.5 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 68 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 41 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 25.5 percent / aq. NaOH / 16 h / Heating 9.1: 37 percent / aq. HCl / diethyl ether / 4 h 10.1: DCC / tetrahydrofuran / 0 - 20 °C 10.2: tetrahydrofuran / 24 h / 20 °C 11.1: 0.09 g / tetrahydrofuran / 24 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 11 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 73 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 59 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 45 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 78.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 71 percent / aq. NaOH / 16 h / Heating 9.1: 60 percent / aq. HCl / diethyl ether / 4 h 10.1: DCC / tetrahydrofuran / 0 - 20 °C 10.2: tetrahydrofuran / 24 h / 20 °C 11.1: 89 mg / tetrahydrofuran / 24 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 89.6 percent / K2CO3; (n-Bu)4NI / 7 °C / Heating 3.1: 65 percent / Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 5 h / Heating 4.1: 79 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 5.1: 83.5 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 6.1: 25 percent / aq. NaOH / 16 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 89.6 percent / K2CO3; (n-Bu)4NI / 7 °C / Heating 3.1: 65 percent / Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 5 h / Heating 4.1: 79 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 5.1: 79 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 6.1: 25 percent / aq. NaOH / 16 h / Heating 7.1: 51 percent / aq. HCl / diethyl ether / 4 h 8.1: DCC / tetrahydrofuran / 0 - 20 °C 8.2: tetrahydrofuran / 24 h / 20 °C 9.1: 0.11 g / tetrahydrofuran / 24 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: NaI; NaOH / methanol 1.2: 35 percent / aq. NaClO / 1 h / 0 - 2 °C 2.1: 84 percent / triethylamine; DMAP / toluene / 8 h / Heating 3.1: Pd(PPh3)4; aq. NaHCO3 / 1,2-dimethoxy-ethane / 8 h / Heating 3.2: 73 percent / aq. NaOH / ethanol 4.1: 99 percent / pyridine / 24 h / 20 °C 5.1: 59 percent / Pd(PPh3)4; Na2CO3 / toluene / 8 h / Heating 6.1: 45 percent / cyclohexene / Pd(OH)2/C / methanol / Heating 7.1: 82 percent / K2CO3; (n-Bu)4NI / acetonitrile / Heating 8.1: 64 percent / aq. NaOH / 16 h / Heating 9.1: 68 percent / aq. HCl / diethyl ether / 4 h 10.1: DCC / tetrahydrofuran / 0 - 20 °C 10.2: tetrahydrofuran / 24 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: KOH / ethanol / 6 h / Heating 2: H2 / 10 percent Pd/C / ethyl acetate / 4 h / 25 °C / 2280 Torr | ||
Multi-step reaction with 2 steps 1: 72 percent / 4 N NaOH / dimethylsulfoxide / 1 h / 75 °C 2: 93 percent / H2 / 10percent Pd/C / tetrahydrofuran; methanol / 760 Torr / Heating | ||
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 48 h / 80 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / ethyl acetate / 2 h / 20 °C / 1500.15 Torr / Inert atmosphere |
Multi-step reaction with 2 steps 1.1: potassium carbonate / acetone / Inert atmosphere; Reflux 1.2: 20 h / Inert atmosphere; Reflux 2.1: palladium 10% on activated carbon; hydrogen / tetrahydrofuran / 26 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: O-benzylcatechol; 4-Fluoronitrobenzene With potassium carbonate In DMF (N,N-dimethyl-formamide) at 90℃; for 5h; Stage #2: In DMF (N,N-dimethyl-formamide); dichloromethane for 3h; | 2 Preparation 2; 4-(2-Benzyloxyphenoxy)aniline A solution of 2-benzyloxyphenol (6.01 g, 30 mmol) in anhydrous N,N-dimethylformamide (25 mL) was treated with anhydrous potassium carbonate (7.6 g, 55 mmol), then with 4-fluoronitrobenzene (3.53 g, 25 mmol), and heated to 90° C. for 5 h under nitrogen. The solution was cooled to room temperature, diluted with dichloromethane (50 mL), and treated with DOWEX 550A OH anion exchange resin (10 g) which had been washed dry with methanol. The mixture was stirred for 3 h, filtered, and the filtrate concentrated in vacuo (exhaustively at end to remove DMF). The residue was chromatographed on silica gel (eluted with 2:1 hexane/ethyl acetate) to afford 4-(2-benzyloxyphenoxy)nitrobenzene (6.40 g, 66%) as a white solid. [0154] 4-(2-Benzyloxyphenoxy)nitrobenzene (2.57 g, 8 mmol) was dissolved in reagent grade ethanol (20 mL) and treated with concentrated aqueous hydrochloric acid (2.5 mL). The solution was heated to 55° C. under nitrogen, then cautiously treated with iron powder (3.1 g, 55 mmol) in portions with cooling needed after initial exotherm to 75° C. After addition was complete, stirring was continued at 50-60° C. for 45 minutes, then the mixture was cooled to room temperature and filtered through celite (rinse filter cake with dichloromethane). The filtrate was concentrated in vacuo, the residue dissolved in dichloromethane and the solution washed with saturated aqueous sodium carbonate. The organic layer was separated and the aqueous layer extracted with dichloromethane. The combined organic solution was dried (sodium sulfate), concentrated in vacuo, and chromatographed on silica gel (eluted with dichloromethane, then 10% ethyl acetate/dichloromethane, then 20% ethyl acetate/dichloromethane) to afford the title compound (2.22 g, 95%) as a tan solid; mp 111-112.5° C. 1H NMR: 7.30 (m,4H), 7.20-7.30 (m,1H), 6.97 (m,2H), 6.80-6.90 (m,4H), 6.60-6.65 (m,2H), 5.12 (s,2H), 3.50 (br s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate In acetone for 5h; Heating / reflux; | 5 1- (PHENYLMETHOXY)-2- [3- (1, 1, 2, 2-TETRAMETHYL-1-SILAPROPOXY) PROPOXY] BENZENE. (3- BROMOPROPOXYL)-TERT-BUTYLDIMETHYLSILANE (2.18 g, 2.0 ml, 8.61 mmol) is added to a solution OF 2- (BENZYLOXY) phenol (2.15 g, 1.88 ml, 10.76 mmol) and potassium carbonate (1.48 g, 10.76 mmol) in acetone (20 ml). The resulting mixture is refluxed for 5 hours and then cooled to room temperature. The solvents are removed and the residue is dissolved in EtOAc (150 ml) and water (30 ml). The organic layers are dried over NA2S04 and filtered, and the filtrate is concentrated to give a syrup, which is purified by column chromatography with hexane-5% EtOAc/hexane to give the product (2.90 g, 90%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | Stage #1: Ethyl 4-bromobutyrate; O-benzylcatechol With potassium carbonate In ethanol for 8h; Heating / reflux; Stage #2: With sodium hydroxide; ethanol; water at 50℃; for 2h; Stage #3: With hydrogenchloride In water at 0℃; | 9 Compound 175 - 4- (2-Benzyloxy-phenoxy)-butyric; [346] To a 250 mL flask, equipped with a reflux condenser, magnetic stirrer, and under inert atmosphere, was added 2-benzyloxy-phenol (8.0 g, 40 mmol), 4- bromobutanoic acid ethyl ester (5.7 mL, 40 mmol), potassium carbonate (7.2 g, 52 mmol), and ethanol (100 mL). The reaction mixture was heated to reflux with stirring for 8 hours. The reaction was cooled to room temperature and the insoluble byproduct was removed by suction filtration. 2N aqueous sodium hydroxide (30 mL) was added to the filtrate. This solution was heated to 50°C for 2 hours. The solution was cooled to room temperature, the ethanol removed under reduced pressure, and the resulting solution was adjusted to pH 9. The aqueous solution was washed with ethyl acetate (2 X 30 mL) and residual ethyl acetate was removed under reduced pressure. The solution was cooled to 0°C with an external ice bath and then acidified to pH 2 with 6N aqueous hydrochloric acid. The precipitated product was collected by suction filtration and dried under vacuum. The product (7.2 g, 63%) was isolated as a white powder. 1H-NMR (400MHz, DMSO-d6) : No. 12.0, s, 1H (COOH) ; No. 7.4, multiplet, 5H (Benzylic aryl H's) ; No. 7.0, multiplet, 2H (Aryl H's) ; No. 6.9, multiplet, 2H (Aryl H's) ; 6 5.0, s, 2H (Benzylic CH2); 6 4.0, t, 2H (CH2 a to phenoxy) ; No. 2.4, t, 2H (CH2 a to COOH) ; No. 1.9, multiplet, 2H (remaining CH2 group). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Compound 177 - 11-(2-Benzyloxyphenoxy)undecanoic acid:; [349] To a 250 mL Erienmeyer flask was added freshly ground potassium hydroxide (4.2 g, 74.91 mmol) and 100 mL dimethyl sulfoxide. 2-benzyloxy-phenol (5 g, 24.97 mmol) and <strong>[6287-90-7]11-bromoundecanoic acid methyl ester</strong> (7 g, 25.07 mmol) was added and the mixture was allowed to stir at room temperature overnight. Water (75 mL) was added and the solution was heated to 85C , with stirring, for 3 hours. The reaction was cooled to room temperature and acidified with concentrated hydrochloric acid to pH 2. The acidified solution was cooled to 4C for 2 hours, and the precipitate then collect by suction filtration. The product was recrystallized form ethanol/water. The product (8.88 g, 93%) was isolated as a light brown solid, mp 62-63C. Combustion analysis: Found: C 74.71 H 8.08%; C24H3204 requires C 74.97, H 8.39 %; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.9% | With triethylamine In dichloromethane at 0 - 20℃; for 2h; | 2- (Benzyloxy)phenyl methanesulf onate; 2-(Benzyloxy)phenol (3.0Og, 14.98mmol) was dissolved in dry DCM (7OmL) under nitrogen atmosphere and cooled on an ice-water bath. Methanesulfonyl chloride (2.06g, 17.98mmol) was added during stirring followed by TEA (2.27g, 22.47mmol). The reaction mixture was stirred at rt for 2h and then washed with aqueous saurated NaHCO3, dried (MgSO4), filtered and evaporated affording the title compund (4.04g, 96.9%). 1H NMR (500MHz, CDCl3): δ 3.09 (s, 3H), 5.15 (s, 2H), 7.02 (dt, IH), 7.09 (dd, IH), 7.27 (dt, IH), 7.34-7.48 (m, 6H); 13C NMR (125MHz, CDCl3): δ 38.72, 71.37, 114.67, 121.79, 125.06, 127.95, 128.50, 128.68, 129.00, 136.20, 138.96, 150.91. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide | P.3 Production of 2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol INTERMEDIATE PRODUCTION EXAMPLE 3 Production of 2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol First Process: A mixture of 4.05 g of 2-benzyloxyphenol and 9.5 ml of N,N-dimethylformamide was added dropwise into a mixture of 0.80 g of sodium hydride and 20 ml of N,N-dimethylformamide while cooling with ice, and the mixture was stirred for 30 minutes. A mixture of 7.1 g of 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene (described later, produced in Intermediate Production Example 4) and 17 ml of N,N-dimethylformamide was added dropwise at the same temperature, and stirred for 1 hour. This reaction solution was poured into ice water, and extracted with ethyl acetate. The organic layer was washed once with 1N hydrochloric acid and once with saturated saline and dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography to obtain 8.6 g of 2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene. 1H-NMR (CDCl3/250 MHz) δ (ppm): 3.52 (q, 3H, J=1.1 Hz), 5.01 (s, 2H), 6.31 (s, 1H), 6.81 (d, 1H, J=6.0 Hz), 6.9 to 7.1 (m, 2H), 7.1 to 7.4 (m, 7H), 7.78 (d, 1H, J=8.7 Hz) | |
Stage #1: O-benzylcatechol With sodium hydride In DMF (N,N-dimethyl-formamide) at 0℃; for 0.5h; Stage #2: 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene In DMF (N,N-dimethyl-formamide) at 0℃; for 1h; | 1.1 Reference Production Example 1; Step 1 A mixture of 4.05 g of 2-benzyloxyphenol and 9.5 ml of N,N-dimethylformamide was added dropwise to a mixture of 0.80 g of sodium hydride and 20 ml of N,N-dimethylformamide under ice cooling, and the mixture was stirred for 30 minutes. A mixture of 7.1 g of 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyri midin-1-yl]nitrobenzene and 17 ml of N,N-dimethylformamide was added dropwise at the same temperature, and the mixture was stirred for 1 hour. The reaction mixture was poured into ice water, and the mixture was extracted with ethyl acetate. The organic layer was washed once with 1N hydrochloric acid and once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 8.6 g of 2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene. 1H-NMR (CDCl3, 250 MHz) δ(ppm): 3.52 (q, 3H, J = 1.1 Hz), 5.01 (s, 2H), 6.31 (s, 1H), 6.81 (d, 1H, J = 6.0 Hz), 6.9-7.1 (m, 2H), 7.1-7.4 (m, 7H), 7.78 (d, 1H, J = 8.7 Hz). | |
Stage #1: O-benzylcatechol With sodium hydride In DMF (N,N-dimethyl-formamide) at 0℃; for 0.5h; Stage #2: 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene In DMF (N,N-dimethyl-formamide) at 0℃; for 1h; | A mixture of 4.05 g of 2-benzyloxyphenol and 9.5 ml of N,N-dimethylformamide was added dropwise to amixture of 0.80 g of sodium hydride and 20 ml of N,N-dimethylformamide under ice cooling and the mixture was stirredfor 30 minutes. A mixture of 7.1 g of 2,5-difluoro-4-[3-methyl-2,6'-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene and 17 ml of N,N-dimethylformamide was added dropwise at the same temperature and the mixturewas stirred for 1 hour. The reaction solution was poured into ice-water and extracted with ethyl acetate. The organiclayer was washed successively once with 1N-HCl and once with saturated aqueous sodium chloride solution, driedover anhydrous magnesium sulfate and concentrated. The residue was subjected to silica-gel column chromatographyto give 8.6 g of 2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.1H-NMR (CDCl3/250MHz), δ (ppm): 3.52 (q,3H,J=1.1Hz), 5.01 (s,2H), 6.31 (s,1H), 6.81 (d,1H,J=6.0Hz), 6.9-7.1 (m,2H), 7.1-7.4 (m,7H), 7.78 (d,1H,J=8.7Hz). |
Stage #1: O-benzylcatechol With sodium hydride In DMF (N,N-dimethyl-formamide) at 0℃; for 0.5h; Stage #2: 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene In DMF (N,N-dimethyl-formamide) at 0℃; for 1h; | A mixture of 4.05 g of 2-benzyloxyphenol and 9.5 ml of N,N-dimethylformamide was added dropwise to amixture of 0. 80 g of sodium hydride and 20 ml of N,N-dimethylformamide under ice cooling and the mixture was stirredfor 30 minutes. A mixture of 7.1 g of 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene and 17 ml of N,N-dimethylformamide was added dropwise at the same temperature and the mixturewas stirred for 1 hour. The reaction solution was poured into ice-water and extracted with ethyl acetate. The organiclayer was washed successively once with 1N-HCl and once with saturated aqueous sodium chloride solution, driedover anhydrous magnesium sulfate and concentrated. The residue was subjected to silica-gel column chromatographyto give 8.6 g of 2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.1H-NMR (CDCl3/250MHz), d (ppm): 3.52 (q,3H,J=1.1Hz), 5.01 (s,2H), 6.31 (s,1H), 6.81 (d,1H,J=6.0Hz), 6.9-7.1 (m,2H), 7.1-7.4 (m,7H), 7.78 (d,1H,J=8.7Hz). | |
Stage #1: O-benzylcatechol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene In DMF (N,N-dimethyl-formamide) at 0℃; | A mixture of 4.05 g of 2-benzyloxyphenol and 9.5 ml of N,N-dimethylformamide was added dropwise to a mixture of 0.80 g of sodium hydride and 20 ml of N,N-dimethylformamide under ice cooling and the mixture was stirred for 30 minutes. A mixture of 7.1 g of 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobonzene and 17 ml of N,N-dimethylformamide was added dropwise at the same temperature and the mixture was stirred for 1 hour. The reaction solution was poured into ice-water and extracted with ethyl acetate. The organic layer was washed successively once with 1N-HC1 and once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica-gel column chromatography to give 8.6 g of 2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.1H-NHR (CDCl3/250MHz), δ (ppm): 3.52 (q,3H,J=1.1Hz), 5.01 (s,2H), 6.31 (s,1H), 6.81 (d,1H,J=6.0Hz), 6.9-7.1 (m,2H), 7.1-7.4 (m,7H), 7.78 (d,1H,J=8.7Hz). | |
Stage #1: O-benzylcatechol With sodium hydride In DMF (N,N-dimethyl-formamide) at 0℃; for 0.5h; Stage #2: 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene In DMF (N,N-dimethyl-formamide) at 0℃; for 1h; | A mixture of 4.05 g of 2-benzyloxyphenol and 9.5 ml of N,N-dimethylformamide was added dropwise to a mixture of 0.80 g of sodium hydride and 20 ml of N,N-dimethylformamide under ice cooling and the mixture was stirred for 30 minutes. A mixture of 7.1 g of 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene and 17 ml of N,N-dimethylformamide was added dropwise at the same temperature and the mixture was stirred for 1 hour. The reaction solution was poured into ice-water and extracted with ethyl acetate. The organic layer was washed successively once with 1N-HCl and once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica-gel column chromatography to give 8.6 g of 2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.1H-NMR (CDCl3/250MHz), δ (ppm): 3.52 (q,3H, J=1.1Hz), 5.01 (s,2H), 6.31 (s,1H), 6.81 (d,1H, J=6.0Hz), 6.9-7.1 (m,2H), 7.1-7.4 (m,7H), 7.78 (d,1H, J=8.7Hz). | |
Stage #1: O-benzylcatechol With sodium hydride In DMF (N,N-dimethyl-formamide) at 0℃; for 0.5h; Stage #2: 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene In DMF (N,N-dimethyl-formamide) at 0℃; for 1h; | A mixture of 4.05 g of 2-benzyloxyphenol and 9.5 ml of N,N-dimethylformamide was added dropwise to a mixture of 0.80 g of sodium hydride and 20 ml of N,N-dimethylformamide under ice cooling and the mixture was stirred for 30 minutes.. A mixture of 7.1 g of 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene and 17 ml of N,N-dimethylformamide was added dropwise at the same temperature and the mixture was stirred for 1 hour.. The reaction solution was poured into ice-water and extracted with ethyl acetate.. The organic layer was washed successively once with 1N-HCl and once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated.. The residue was subjected to silica-gel column chromatography to give 8.6 g of 2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.1H-NMR (CDCl3/250MHz), δ (ppm): 3.52 (q,3H,J=1.1Hz), 5.01 (s,2H), 6.31 (s,1H), 6.81 (d, 1H,J=6.0Hz), 6.9-7.1 (m,2H), 7.1-7.4 (m,7H), 7.78 (d, 1H, J=8.7Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With sodium nitrate; sulfuric acid In dichloromethane | 97.a a) a) Preparation of 2-nitro-6-benzyloxy phenol 2-Benzyloxyphenol (5.00 g, 25.0 mmol) was dissolved in methylene chloride(40 mL) followed by the addition of sodium nitrate (2.30 g, 27.5 mmol). The addition of sulfuric acid (31 mL/3M) was then made, followed by addition of a catalytic amount of sodium nitrite. The mixture was allowed to stir. After 24 hours, the reaction mixture was diluted with methylene chloride and extracted with water. The organic layer was dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4% MeOH/CH2 Cl2) gave the desired product(2.6 g, 43%). 1 H NMR (CD3COCD3): δ 7.70 (d, 1H), 7.50-7.28 (m, 5H), 7.14 (d, 1H), 6.92 (t, 1H), 5.21 (s, 2H). |
43% | With sodium nitrate; sulfuric acid In dichloromethane | 97 a)Preparation of 2-nitro-6-benzyloxy phenol a)Preparation of 2-nitro-6-benzyloxy phenol 2-Benzyloxyphenol (5.00 g, 25.0 mmol) was dissolved in methylene chloride(40 mL) followed by the addition of sodium nitrate (2.30 g, 27.5 mmol). The addition of sulfuric acid (31 mL/3M) was then made, followed by addition of a catalytic amount of sodium nitrite. The mixture was allowed to stir. After 24 hours, the reaction mixture was diluted with methylene chloride and extracted with water. The organic layer was dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4%MeOH/CH2 Cl2) gave the desired product(2.6 g, 43%). 1 H NMR (CD3COCD3): d 7.70 (d,1H), 7.50-7.28 (m, 5H), 7.14 (d, 1H), 6.92 (t, 1H), 5.21 (s, 2H). |
43% | With sodium nitrate; sulfuric acid In dichloromethane | 97.a a) a) Preparation of 2-nitro-6-benzyloxy phenol 2-Benzyloxyphenol (5.00 g, 25.0 mmol) was dissolved in methylene chloride (40 mL) followed by the addition of sodium nitrate (2.30 g, 27.5 mmol). The addition of sulfuric acid (3 l mL/3M) was then made, followed by addition of a catalytic amount of sodium nitrite. The mixture was allowed to stir. After 24 hours, the reaction mixture was diluted with methylene chloride and extracted with water. The organic layer was dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4%MeOH/CH2CH2) gave the desired product (2.6 g, 43%). 1H NMR (CD3COCD3): d 7.70 (d, 1H), 7.50-7.28 (m, 5H), 7.14 (d, 1H), 6.92 (t, 1H), 5.21 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
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With potassium carbonate In ethyl acetate; acetone | 1 Synthesis of 4-(2-(11-Carboxyundecyloxy)phenoxy)-butyric acid (7) STR67 A. Ethyl 4-(2-Benzyloxyphenoxy)-butyrate (3) To a stirred solution of 2-benzyloxyphenol (1) (4.0 g, 20 nM) and ethyl 4-bromobutyrate (2) (5.6 g, 28.7 mM) in dried acetone (100 mL) was added anhydrous ground potassium carbonate (6.0 g, 44 mM) and the resultant mixture heated at reflux under nitrogen until TLC analysis showed the absence of the starting phenol. Flash chromatography (silica gel, 15% ethyl acetate/hexane as eluant) of the filtered and concentrated mixture yielded 3.0 g of product (3) as a clear oil. When the ethyl 4-bromobutyrate is replaced by halo-esters in the above example, the corresponding ether-ester is obtained. | |
With potassium carbonate In ethyl acetate; acetone | 1 Synthesis of 4-(2-(11-Carboxyundecyloxy)phenoxy)butyric acid (7) STR68 A. Ethyl 4-(2-Benzyloxyphenoxy)-butyrate (3) EXAMPLE 1 Synthesis of 4-(2-(11-Carboxyundecyloxy)phenoxy)butyric acid (7) STR68 A. Ethyl 4-(2-Benzyloxyphenoxy)-butyrate (3) To a stirred solution of 2-benzyloxyphenol (1) (4.0 g, 20 nM) and ethyl 4-bromobutyrate (2) (5.6 g, 28.7 mM) in dried acetone (100 mL) was added anhydrous ground potassium carbonate (6.0 g, 44 mM) and the resultant mixture heated at reflux under nitrogen until TLC analysis showed the absence of the starting phenol. Flash chromatography (silica gel, 15% ethyl acetate/hexane as eluant) of the filtered and concentrated mixture yielded 3.0 g of product (3) as a clear oil. | |
With potassium carbonate In ethyl acetate; acetone | 1.A A. A. Ethyl 4-(2-Benzyloxyphenoxy)-butyrate (3) To a stirred solution of 2-benzyloxyphenol (1) (4.0 g, 20 nM) and ethyl 4-bromobutyrate (2) (5.6 g, 28.7 mM) in dried acetone (100 mL) was added anhydrous ground potassium carbonate (6.0 g, 44 mM) and the resultant mixture heated at reflux under nitrogen until TLC analysis showed the absence of the starting phenol. Flash chromatography (silica gel, 15% ethyl acetate/hexane as eluant) of the filtered and concentrated mixture yielded 3.0 g of product (3) as a clear oil. When the ethyl 4-bromobutyrate is replaced by halo-esters in the above example, the corresponding ether-ester is obtained. |
Yield | Reaction Conditions | Operation in experiment |
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70% | Stage #1: O-benzylcatechol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: [2H3]methyl methanesulfonate In N,N-dimethyl-formamide at 20℃; for 16h; | 3.1; 4.1 EXAMPLE 3; d3-4-tert-Butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-[2,2']bipyrimidinyl-4-yl]-benzenesulfonamide Step 1 d3-1-benzyloxy-2-methoxybenzene: 2-benzyloxyphenol (15 g, 75 mmol) was added to sodium hydride (4.5 g, 113 mmol) suspended in dry N,N-dimethylformamide (250 mL) at about 0° C. Under continuous stirring, the reaction mixture was maintained at about 0° C. for about 30 minutes and d3-methyl methanesulfonate (1.5 equiv) was added dropwise, the reaction mixture was then maintained at ambient temperature for about 16 hours. The reaction mixture was quenched with water (50 mL), and the crude product, a yellow oil, was isolated using standard extractive work up, and purified by column chromatography on silica gel to give the title compound (11.38 g, 70%). 1H NMR (300 MHz, CDCl3) δ 5.17 (s, 2H), 6.85-6.94 (4H, m), 7.27-7.47 (5H, m); E1-MS m/z=218 (M+). EXAMPLE 4d7-4-tert-Butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-[2,2']bipyrimidinyl-4-yl]-benzenesulfonamide Step 1 d3-1-benzyloxy-2-methoxybenzene: The title compound was made by following the procedure set forth in Example 3, step 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With sulfuryl dichloride In toluene at 20℃; for 1h; | |
With sulfuryl dichloride In toluene at 0 - 20℃; | 29.i Sulfuryl chloride (0. 965ML) was added to a stirred solution OF 2- (BENZYLOXY) phenol (2. 0g) in dry toluene (20ML) at 0°C. The mixture was warmed to RT and stirred overnight then cooled to 0°C and quenched with ice-water before extracting with ethylacetate. The organics were dried, evaporated under reduced pressure and the residue purified by chromatography on silica eluting with DCM/isohexane (1: 1). Yield 1.5g MS: ESI (-ve) 233 (M-1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: O-benzylcatechol With sodium hydride In diethyl ether Stage #2: 3-(tetrahydro-2H-pyran-2-yloxy)propyl bromide In diethyl ether at 70℃; for 5h; | 3 1-(3-perhydro-2H-pyran-2-yloxypropoxy)-2-(phenylmethoxy)benzene: Sodium hydride (10 mmol) is added to a solution OF 2- (PHENYLMETHOXY) phenol (9 mmol) in 50 mL of dry ether, and subsequently treated with 12 mmol OF 3-BROMO-1-PERHYDRO-2H-PYRAN-2- yloxypropane in 10 mL of ether. The mixture is stirred at 70 C for 5 hours, then quenched by the addition of 2 mL of methanol followed by partitioning between ethyl acetate and water. The organic phase is washed with brine, dried, concentrated, and the crude residue is purified on a silica gel column, eluting with 5% ethyl acetate in hexane, to obtain the product as a clear oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: O-benzylcatechol; benzyl 2-bromobenzoate With pyridine; potassium carbonate at 130℃; for 0.5h; Inert atmosphere; Stage #2: at 150℃; for 20h; | 74 2-Benzyloxy-phenol (200mg, 1mmol), 2-Bromo-benzoic acid benzyl ester (291mg, 1mmol) and potassium carbonate (201mg, 1.8mmol) were charged into a three-neck round bottom flask containing 2ml of dry pyridine. The reaction mixture was heated at 130°C for 0.5h under nitrogen protection. CuO (16mg, 0.2mmol) was added to the mixture. The temperature was raised to 150°C and the reaction was stirred at that temperature for 20h. Upon completion, the reaction mixture was cooled to room temperature and then it was poured into ice water, acidified to a pH of 6 with 2N HC1. The solution was extracted with ethyl acetate. The organic layer was washed with saturated brine solution, dried over anhydrous MgSO4, filtered and evaporated by a rotatory evaporator. After chromatographic purification on silica, a colorless oil was obtained. 1HNMR (300MHz, CDCl3): δ 5.04 (s, 2H), 5.33 (s, 2H), 6.81 (d, 1H), 7.03 (m, 7H), 7.18 (m, 4H), 7.25 (m, 3H), 7.37 (m, 2H), 7.93 (d, 1H, J =7.8 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With potassium carbonate In acetone Reflux; | 4.1.8. General procedure for the preparation of compounds 21a-e, 22a-e, and 23a-d General procedure: K2CO3 (1 equiv) and substituted benzyl bromine (1.1 equiv) were sequentially added to a solution of phenols 19a-d, anilines 16a-e, or methanesulfonamides 17a-e (1.0 equiv) in acetone/acetonitrile, and the mixture was stirred under reflux from 3 h to overnight. Then, the reaction mixture was cooled to room temperature and filtered. The filtrate was evaporated to give a crude product, which was purified using flash chromatography with hexane-EtOAc to give the desired final product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With copper(l) iodide; N,N-dimethylglycine hydrochoride; caesium carbonate In 1,4-dioxane at 90℃; for 48h; Inert atmosphere; Sealed tube; | |
42% | With copper(l) iodide; N,N-dimethylglycine hydrochoride; caesium carbonate In 1,4-dioxane at 90 - 100℃; for 48h; Inert atmosphere; Sealed tube; | 1.1 Step 11 General procedure: A solution of indole (1.0 equiv), phenol (1.3 equiv), Cs2CO3 (1.5 euqiv), CuI (0.1 equiv) and N,N-dimethylglycine hydrochloride (0.3 equiv) in dry dioxane (5.0 mL per indole intermediate) was stirred at 90-100° C. under N2 atmosphere in a sealed tube for 48 h. The reaction was cooled down, quenched with brine, and extracted with ethyl acetate (3×10 mL). The combined organic layer was dried over anhydrous Na2SO4, concentrated by rotary evaporation, and purified by column chromatography to give 54a-c. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With potassium carbonate In N,N-dimethyl-formamide at 100 - 120℃; for 12h; Inert atmosphere; | |
69% | With potassium carbonate In N,N-dimethyl-formamide at 100 - 110℃; Inert atmosphere; | 3.1 Step 1 General procedure: A solution of benzylaldehyde (1.0 equiv), 2-benzyloxyphenol (1.0 equiv), and K2CO3 (1.5 equiv) in dry DMF (3.0 mL per mmol benzyaldehyde) were stirred at 100-110° C. under N2 atmosphere overnight. The reaction was cooled down, quenched with 1N HCl, and extracted with ethyl acetate (3×15 mL). The combined organic layer was dried over anhydrous Na2SO4, concentrated by rotary evaporation and purified by column chromatography to give 18a-c. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With trifluoroacetic anhydride In dichloromethane at 25℃; for 0.5h; | Typical Procedure for Syntheses of Benzofurans General procedure: In a reaction flask, 4-tert-butylphenol (30 mg, 0.20mmol) and 1a (51 mg, 0.24mmol) were dissolved in dichloromethane (2 mL). Trifluoroacetic anhydride (33 L, 0.24mmol) was added to the solution at 25 °C. After being stirred for 30 min, the mixture was filtered through a pad of alumina and the filtrate was concentrated. Chromatographic purification on silica gel (hexane/CH2Cl2 = 5/1) yielded 5-(tert-butyl)-2-methylsulfanyl-3-phenylbenzo[b]furan (2a, 51 mg, 0.17mmol, 87%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With triethylamine In dichloromethane at 35℃; for 3.5h; Inert atmosphere; | Carbamate 8. Carbamate 8 was prepared using a known procedure with minor modifications. To a solution of 2-benzyloxyphenol (7, 1.30 g, 6.50 mmol, 1.00 equiv) in DCM (22 mL) was added isopropyl isocyanate (1.60 mL, 16.0 mmol, 2.50 equiv) and Et3N (0.36 mL, 2.6 mmol,0.40 equiv). The reaction mixture was stirred at 35 °C for 3.5 h. After cooling to room temperature, the solution was concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (1% TEA in heptane) to give carbamate 8 (1.50 g, 5.26mmol, 81% yield) as a white powder. 1H NMR (400 MHz, CDCl3): δ 7.42 (dd, J = 7.8, 1.0, 2H),7.39-7.26 (m, 3H), 7.16-7.07 (m, 2H), 7.03 - 6.90 (m, 2H), 5.08 (s, 2H), 4.79 (s, 1H), 3.97-3.77(m, 1H), 1.17 (d, J = 6.5, 6H); HRMS (ESI, Pos): calcd for C17H20NO3 [M+H]+: 286.1438 m/z,found: 286.1436 m/z. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 58.1% 2: 34% | With ammonium cerium (IV) nitrate In acetonitrile at -5 - 0℃; for 3h; | Nitration of III with CAN A solution of (NH4)2Ce(NO3)6 (10g, 18.2 mmol) in acetonitrile (60 mL) was added drop-wise to a stirred solution of 2-benzyloxyphenol (5g, 25.0 mmol) in acetonitrile (40 mL) cooled at 5 °C. The reaction mixture was stirred for 3 h at 0 °C and then diluted with water and extracted with ethyl acetate. The organic phase was concentrated and the resulting residue was purified on silica gel (cyclohexane/ethyl acetate 8/2) to give, in sequence, 1a (3.56 g, 58.1%) and 1c (2.08 g, 34.0%) as yellow solids. Analytical data for 1a and 1c are reported in Table 1 and in the Supporting information. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 35% 2: 30% 3: 12% | With sodium nitrate; sulfuric acid; sodium nitrite In dichloromethane at -10℃; for 3h; | Nitration of III with sodium nitrate and sulfuric acid Sodium nitrate (2.30 g, 27.05 mmol), 3 M sulfuric acid (31 mL), and sodium nitrite (10 mg) were sequentially added to a stirred solution of 2-benzyloxyphenol (5g, 25.0 mmol) in DCM (40 mL) cooled at 10 °C. The reaction mixture was stirred for 3h at the same temperature, then diluted with DCM and washed with water. The organic phase was concentrated and purified on silica gel (cyclohexane/ethyl acetate 8/2) to give, in sequence, 1a (2.15 g, 35%) and 1c (1.84g, 30%) as yellow solids and 1e (0.87 g, 12%) as a brown solid. Analytical data for 1a, 1c, and 1e are reported in Table 1 and in the Supporting information. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of 5.0 g (29 mmol) <strong>[2879-42-7]3-chloro-2,5,6-trifluoropyridine</strong> (CAS 2879-42-7) in 50 ml_ DMSO was added 2.1 g (33 mmol) NaN3 and the solution was stirred at room temperature for 3 hours. Then 19.5 g (60 mmol) CS2CO3 was added followed by a solution of 6.2 g (31 mmol) 2- (Benzyloxy)phenol) in 40 ml. DMSO. The mixture was stirred at room temperature for 16 hours, water was added and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous Na2S04, filtered and the solvent was removed under reduced pressure. The crude material (15 g) was used without further purifiction in the next step [M+H] = 371.0; Rt = 1 .368 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.202 g | Stage #1: benzyl 4-((tert-butoxycarbonyl)amino)-2-(3-((methylsulfonyl)oxy)propyl)benzoate With triethylamine In tetrahydrofuran at 0 - 35℃; for 1h; Stage #2: O-benzylcatechol With potassium carbonate In N,N-dimethyl-formamide at 10 - 80℃; | 68.A A) Benzyl 2-(3-(2-(benzyloxy)phenoxy)propyl)-4-((tert-butoxycarbonyl)amino)benzoate A) Benzyl 2-(3-(2-(benzyloxy)phenoxy)propyl)-4-((tert-butoxycarbonyl)amino)benzoate Methanesulfonyl chloride (0.221 mL) and triethylamine (0.904 mL) were added to a mixture of benzyl 4-((tert-butoxycarbonyl)amino)-2-(3-((methylsulfonyl)oxy)propyl)benzoate (1.0 g) and THF (15 mL) at 0° C., followed by stirring at room temperature for 1 hour. A saturated ammonium chloride aqueous solution was added to the reaction mixture at 0° C., followed by extraction with ethyl acetate. The organic layer was washed with a saturated saline solution and was then dried over anhydrous sodium sulfate, and the solvent was distilled under reduced pressure. Potassium carbonate (0.895 g) was added to a mixture of the crude product (1.3875 g) of benzyl 4-((tert-butoxycarbonyl)amino)-2-(3-((methylsulfonyl)oxy)propyl)benzoate, 2-(benzyloxy)phenol (0.454 mL), and DMF (12 mL) at room temperature, followed by stirring at 80° C. overnight. Ethyl acetate and 1 N hydrochloric acid were added to the reaction mixture at 0° C., followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated saline solution and was then dried over anhydrous sodium sulfate, and the solvent was distilled under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (1.202 g). MS: [M+Na]+ 590.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 29.5 %Chromat. 2: 18.6 %Chromat. | With hydrogen In hexane at 260℃; for 10h; Autoclave; | |
1: 39.6 %Chromat. 2: 33.4 %Chromat. | With sulfuric acid; 5% active carbon-supported ruthenium; ethylene glycol at 185℃; for 0.5h; | |
1: 72 %Chromat. 2: 72 %Chromat. | With isopropyl alcohol at 260℃; for 4h; Autoclave; Inert atmosphere; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With potassium hydroxide In water; acetonitrile at -78 - 20℃; | B B. 1 -(Benzyloxy)-2-(difluoromethoxy)benzene To a stirred, cooled (-78 °C) solution of 2-(benzyloxy)phenol (Intermediate 1 16A) (2.50 g, 12.5 mmol) and potassium hydroxide (14.0 g, 250 mmol) in acetonitrile (120 mL) and water (120 mL) was added diethyl (bromodifluoromethyl)phosphonate (4.44 mL, 25.0 mmol). The cooling bath was removed and the mixture was allowed to warm to room temperature. After stirring overnight, the mixture was extracted twice with Et20. The combined organic layers were washed with brine, dried over Na2S04, filtered and concentrated. The residue was purified on silica gel eluting with a 0%-50% EtOAc in hexanes gradient to give the title compound (1 .54 g, 49%). 1H NMR (400 MHz, CD3SOCD3) δ 5.15 (s, 2 H), 6.87-7.00 (m, 2 H), 7.07 (t, J = 76 Hz, 1 H), 7.12-7.49 (m, 7 H); LC-MS (LC-ES) M-H = 249. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With tetrakis(actonitrile)copper(I) hexafluorophosphate; N,N'-di-tert-butylethylenediamine; oxygen In dichloromethane at 20℃; for 4h; | General Procedure B General procedure: A flame-dried, 25 mL Radley tube, equipped with a Teflon coated stir bar and a rubber septum, was charged with phenol (1.0 mmol, 1.0 equiv.). The reaction vessel was then purged with a steady stream of N2 for 2 min prior to the addition of dry and degassed CH2Cl2 (9.0 mL). A separate, flame-dried test tube (16 x 125 mL) was charged with [Cu(CH3CN)4](PF6) (14.9 mg, 0.04 mmol, 0.04 equiv.), N,N’-di-tert-butylethelenediamine (11 μL, 0.05 mmol, 0.05 equiv.) and CH2Cl2 (1.0 mL) to afford a homogeneous, pink solution. This solution was then added to the Radley tube via syringe to afford a final volume of 10.0 mL and a concentration of 0.1 M with respect to the phenol. The rubber septum was then rapidly removed and replaced with a Radley cap, which was connected to a tank of O2 and pressurized to 1 atm. Under a constant O2 pressure (1 atm), the reaction was vented 3 times for 10 s to eliminate N2. The reaction mixture was then stirred at room temperature for 4 h, depressurized by opening to the atmosphere and quenched by the addition of NaHSO4 (20 mL, 10% by weight aqueous solution), the phases were separated, and the aqueous phase was extracted with CH2Cl2 (3 x 20 mL). The combined organic fractions were then dried over MgSO4, filtered and concentrated in vacuo to afford a residue which was analyzed directly by 1H-NMR. The crude reaction mixture was purified using a Biotage IsoleraTM One (10% EtOAc in hexanes) to afford the quinone product. The synthesis was carried out using general procedure B using S7 (200.24 mg, 1.0 mmol, 1.0 equiv.) to afford 10b (112.7 mg, 0.22 mmol) in 67% isolated yield. Rf (EtOAc/Hexane 1:4) = 0.35; 1H NMR (300 MHz, CDCl3): δ = 7.33-7.27 (m, 9H), 7.25-7.22 (m, 3H), 7.10-7.06 (m, 4H), 7.00 (dt, J = 1.56 Hz, 7.82 Hz, 2H), 5.49 (s, 2H), 5.07 (s, 4H) ppm; 13C NMR (75 MHz, CDCl3): δ = 179.1, 163.2, 149.4, 141.2, 136.1, 128.6, 128.1, 127.9, 127.2, 122.3, 121.7, 114.9, 106.0, 70.8 ppm. HRMS Calc. for C32H25O6 [M+H]+ = 505.1651 m/z, found [M+H]+ = 505.1854 m/z |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With aluminium(III) iodide; dimethyl sulfoxide In acetonitrile at 80℃; for 18h; | Cleavage of Catechol Monoalkyl Ethers by Aluminum Triiodide- Dimethyl Sulfoxide; General Procedure General procedure: To a suspension of AlI3 (5.5 mmol, 1.1 equiv) in MeCN was added anhyd DMSO (0.430 g, 5.5 mmol, 1.1 equiv). After stirring for 0.5 h at 80 °C, the selected substrate (5 mmol) was added in one portion. The mixture was stirred overnight (18 h) at that temperature before quenching with aq 2 M HCl (10 mL). After extraction with EtOAc (3 50 mL), the organic phases were combined, washed with sat. aq Na2S2O3 and brine, and dried (MgSO4). The solvents were removed on a rotary evaporator, and the residue was purified by column chromatography to give the relevant catechol or phenol. |
63% | With aluminium(III) iodide; <i>N</i>,<i>N</i>-dimethyl-formamide dimethyl acetal In acetonitrile at 80℃; for 18h; | |
63% | With aluminium(III) iodide; <i>N</i>,<i>N</i>-dimethyl-formamide dimethyl acetal In acetonitrile at 80℃; for 18h; | 14 Example 14 (2-Benzyloxyphenol debenzylation) Add acetonitrile (20ml), aluminum triiodide (0.896g, 2.2mmol) and N,N-dimethylformamide dimethyl acetal (0.358g, 3mmol) into a 100ml round-bottomed flask, and stir at 80°C 15min, add 2-benzyloxyphenol (0.400g, 2mmol), continue stirring at 80°C for 18h, after the reaction is complete, it is quenched with 2M dilute hydrochloric acid (10ml), then extracted with ethyl acetate (50ml) three times, and the organic Phase, first washed with saturated sodium thiosulfate aqueous solution (10ml), then dried over anhydrous magnesium sulfate, filtered, the filtrate was removed with a rotary evaporator to remove the solvent, and the residue was passed through flash column chromatography (eluent is petroleum ether/ethyl acetate Ester=4:1, volume ratio) was purified to obtain 0.140 g of catechol (white solid, yield 63%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 48h; Inert atmosphere; | Diethyleneglycol mono-2-benzyloxyphenyl ether 3 A solution of 2-(benzyloxy)phenol (34.4 g, 172 mmol),2-(2-chloroethoxy)ethanol (25.7 g, 206 mmol), and potassiumcarbonate (28.5 g, 206 mmol) in DMF (200 mL) wasstirred at 80°C for 48 h under an argon atmosphere. DMFwas evaporated in vacuo, and the residue was dissolved inethyl acetate, washed with brine, dried over anhydrousmagnesium sulphate, and concentrated. The residue waspuri+ed by silica gel column chromatography (eluent:ethyl acetate/hexane = 1:2 (v/v)) to give 27.7 g (56%) of3 as a pale yellow oil.1H NMR (CDCl3, 400 MHz): M 7.46-7.29 (m, 5H), 6.94-6.88 (m, 4H), 5.09 (s, 2H), 4.19-3.57 (m, 8H) ppm. 13C NMR(CDCl3, 100 MHz): M 149.0, 148.9, 137.3, 128.6, 128.0,127.6, 121.9, 121.8, 115.0, 114.8, 72.9, 71.3, 69.7, 69.0,61.7 ppm. HRMS (ESI-TOF) Calcd. for C17H20Na1O4:311.1259 ([M+ Na]+); Found: 311.1261 [M+ Na]+. |
Tags: 6272-38-4 synthesis path| 6272-38-4 SDS| 6272-38-4 COA| 6272-38-4 purity| 6272-38-4 application| 6272-38-4 NMR| 6272-38-4 COA| 6272-38-4 structure
[ 4383-06-6 ]
3-Hydroxy-4-methoxybenzyl alcohol
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[ 61439-59-6 ]
2-(4-(Benzyloxy)phenyl)ethanol
Similarity: 0.87
[ 13807-89-1 ]
2-((4-Methoxybenzyl)oxy)ethanol
Similarity: 0.87
[ 4383-06-6 ]
3-Hydroxy-4-methoxybenzyl alcohol
Similarity: 0.92
[ 61439-59-6 ]
2-(4-(Benzyloxy)phenyl)ethanol
Similarity: 0.87
[ 13807-89-1 ]
2-((4-Methoxybenzyl)oxy)ethanol
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