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Product Details of [ 1131-62-0 ]

CAS No. :1131-62-0 MDL No. :MFCD00008737
Formula : C10H12O3 Boiling Point : -
Linear Structure Formula :- InChI Key :IQZLUWLMQNGTIW-UHFFFAOYSA-N
M.W : 180.20 Pubchem ID :14328
Synonyms :

Calculated chemistry of [ 1131-62-0 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.3
Num. rotatable bonds : 3
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 49.62
TPSA : 35.53 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.38 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.19
Log Po/w (XLOGP3) : 1.44
Log Po/w (WLOGP) : 1.91
Log Po/w (MLOGP) : 1.13
Log Po/w (SILICOS-IT) : 2.19
Consensus Log Po/w : 1.77

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.01
Solubility : 1.77 mg/ml ; 0.00982 mol/l
Class : Soluble
Log S (Ali) : -1.79
Solubility : 2.91 mg/ml ; 0.0162 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.99
Solubility : 0.186 mg/ml ; 0.00103 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.5

Safety of [ 1131-62-0 ]

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:

Application In Synthesis of [ 1131-62-0 ]

* 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.

  • Upstream synthesis route of [ 1131-62-0 ]
  • Downstream synthetic route of [ 1131-62-0 ]

[ 1131-62-0 ] Synthesis Path-Upstream   1~21

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Reference: [1] Heterocycles, 2016, vol. 92, # 10, p. 1882 - 1887
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Reference: [1] Heterocycles, 2016, vol. 92, # 10, p. 1882 - 1887
  • 3
  • [ 1131-62-0 ]
  • [ 105-58-8 ]
  • [ 4687-37-0 ]
YieldReaction ConditionsOperation in experiment
76% With sodium hydride In toluene; mineral oil General procedure: The substrate b-ketoesters 10 a–n were either purchased or synthesized following published procedures. Some benzoylacetates were commercially available. Ethyl 3-oxo-3-phenyl propanoate (10a) was purchased. The reaction of benzoylacetates 10 b–n was prepared as described in previous reports. 25–27 A solution of a substituted acetophenone 8 a–n (0.05 mol) dissolved in toluene (50 mL) was added dropwise to a solution containing diethyl carbonate (9) (0.10 mol) and sodium hydride (0.15 mol 60percent dispersion in mineral oil). The mixture was stirred at room temperature, and then refluxed for 30 min. The mixture was poured into ice water,acidified with glacial acetic acid, and extracted with EtOAc (3x100 mL). The EtOAc extract was then dried over anhydrous MgSO4. After removal of the solvent in vacuo, the crude products were purified by silica gel column chromatography eluting with dichloromethane to afford benzoylacetates 10 b–n. All synthetic compounds were in agreement with 1H NMR, 13C NMR, IR and mass spectroscopic data.
Reference: [1] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5064 - 5075
[2] Heterocycles, 1979, vol. 13, p. 239 - 246
[3] Journal of Medicinal Chemistry, 1997, vol. 40, # 20, p. 3217 - 3227
[4] Patent: JP2005/82549, 2005, A, . Location in patent: Page/Page column 19-20
[5] Angewandte Chemie - International Edition, 2011, vol. 50, # 32, p. 7304 - 7307
[6] Organic and Biomolecular Chemistry, 2015, vol. 13, # 11, p. 3243 - 3254
[7] European Journal of Organic Chemistry, 2015, vol. 2015, # 17, p. 3656 - 3660
[8] Tetrahedron Letters, 2016, vol. 57, # 27-28, p. 3024 - 3028
  • 4
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  • [ 4687-37-0 ]
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Reference: [1] Synthetic Communications, 2007, vol. 37, # 10, p. 1665 - 1673
  • 5
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  • [ 38480-94-3 ]
  • [ 1131-62-0 ]
Reference: [1] Chinese Journal of Chemistry, 2010, vol. 28, # 2, p. 273 - 284
  • 6
  • [ 91-16-7 ]
  • [ 64-19-7 ]
  • [ 38480-94-3 ]
  • [ 1131-62-0 ]
Reference: [1] Chinese Journal of Chemistry, 2010, vol. 28, # 2, p. 273 - 284
  • 7
  • [ 91-16-7 ]
  • [ 141-78-6 ]
  • [ 38480-94-3 ]
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Reference: [1] Chinese Journal of Chemistry, 2010, vol. 28, # 2, p. 273 - 284
  • 8
  • [ 1131-62-0 ]
  • [ 6100-74-9 ]
YieldReaction ConditionsOperation in experiment
47% at 65℃; for 46 h; A solution of ketone 6b (12.5 g, 69.5 mmol) in concentrated H2SO4 (62.5 mL) wasstirred at 65 °C for 46 h. After cooling the reaction mixture to ambient temperature, it was poured onto ice (250 g) and stirred for 1 h.The precipitate was filtered off, washed with water and redissolved in 1M aqueous NaOH (16 mL, 160 mmol). The mixture wasextracted with DCM (65 mL). The aqueous layer was acidified with concentrated HCl (25 mL), stirred for 1.5 h and the precipitatewas filtered off to give 5.39 g (47percent) of the phenol as brown solid with mp 80–81 °C (lit. [11] reports 88–90 °C). 1H NMR data are inaccordance with those published in ref.[11].
46.2% at 62 - 64℃; for 48 h; Dimethoxyacetophenone derivative (I) (72.08 g; 0.4 mol) was dissolved in sulfuric acid (360 ml), and then the mixture was stirred at 62 - 64 °C for 48 h. The reaction mixture was cooled to room temperature, poured into ice water (prepared from 2 kg of ice and 1.6 kg of water) and kept in a refrigerator overnight. The product was collected by filtration, washed with water (5x100 ml) and dried in vacuum at 40 °C until constant weight to obtain the product (40.4 g; 60.2 percent; HPLC purity: 96.4 percent). The crude product was dissolved in warm ethanol (80 ml) and precipitated by addition of n-heptane (80 ml). The mixture was cooled to 0 - 10 °C, stirred at this temperature for 1 h, the product was collected, washed with n-heptane (40 ml) and dried in a vacuum at 40°C until constant weight to obtain the purified product (30.77 g; 46.2 percent; HPLC purity: 99.5 percent).
Reference: [1] Organic Letters, 2017, vol. 19, # 11, p. 2877 - 2880
[2] Phytochemistry (Elsevier), 1991, vol. 30, # 7, p. 2438 - 2439
[3] European Journal of Organic Chemistry, 2006, # 17, p. 4044 - 4054
[4] Beilstein Journal of Organic Chemistry, 2015, vol. 11, p. 884 - 892
[5] Journal of Heterocyclic Chemistry, 2018, vol. 55, # 3, p. 670 - 684
[6] Patent: WO2017/59040, 2017, A1, . Location in patent: Paragraph 0076
[7] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 971 - 977
[8] Collection of Czechoslovak Chemical Communications, 1987, vol. 52, # 4, p. 980 - 988
[9] Patent: US2007/259868, 2007, A1, . Location in patent: Page/Page column 16
[10] Patent: US2008/103168, 2008, A1, . Location in patent: Page/Page column 19
  • 9
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  • [ 498-02-2 ]
Reference: [1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1982, vol. 21, # 3, p. 186 - 188
[2] Patent: WO2006/61666, 2006, A2, . Location in patent: Page/Page column 22-23
  • 10
  • [ 1197-09-7 ]
  • [ 74-88-4 ]
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Reference: [1] Heterocycles, 1997, vol. 44, # 1, p. 139 - 142
[2] Heterocycles, 1997, vol. 44, # 1, p. 139 - 142
  • 11
  • [ 91-16-7 ]
  • [ 75-36-5 ]
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Reference: [1] Journal of the American Chemical Society, 1980, vol. 102, # 9, p. 3056 - 3062
[2] Journal of the American Chemical Society, 1980, vol. 102, # 9, p. 3056 - 3062
  • 12
  • [ 1131-62-0 ]
  • [ 13909-73-4 ]
Reference: [1] Tetrahedron Letters, 1992, vol. 33, # 52, p. 8133 - 8136
  • 13
  • [ 1131-62-0 ]
  • [ 1835-02-5 ]
YieldReaction ConditionsOperation in experiment
83% With benzyltrimethylazanium tribroman-2-uide In methanol; dichloromethane for 16 h; To a stirred solution of 1 -(3,4-dimethoxyphenyl)ethanone (1 .0 g, 5.55 mmol) in dichloromethane (6 mL) and methanol (3 mL) was added benzyltrimethylammonium tribromide (2.16 g, 5.55 mmol). After16 h, the mixture was diluted with dichloromethane (80 mL) and water (40 mL), the organic layer wasseparated, and the water phase was extracted with dichloromethane (80 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated to give 2-bromo-1 -(3,4-dimethoxyphenyl)ethanone (1.20 g, 4.63 mmol, 83 percent) as a brown solid. 1H NMR (400 MHz, ODd3) O 7.63 (s, 1 H), 7.57 (d, J2.1 Hz, 1 H), 6.94 (d, J8.4 Hz, 1 H), 4.43 (s, 2H), 3.98 (d, J8.4 Hz, 6H).
78% With N-Bromosuccinimide; toluene-4-sulfonic acid In acetonitrile at 85℃; for 4 h; General procedure: A mixture of substituted arylethanones 14a-i (10 mmol), N-bromosuccinimide (1.4 g, 12 mmol) and p-toluenesulphonic acid (2.8 g, 15 mmol) in acetonitrile (50 mL) was stirred at 85 °C for 4 h. After completion of reaction (indicated by TLC), the reaction mass was allowed to reach ambient temperature and evaporated excess of acetonitrile under reduced pressure. The residue so obtained was mixed in water, extracted with ethyl acetate (2 × 50 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuuo. The crude product obtained was recrystallized from n-hexane to afford pure 1-aryl-2-bromoethanones 15a-i in 75-85percent yields.
73% With bromine In diethyl ether; chloroform at 0 - 20℃; for 2.5 h; Step 1. 2-Bromo-1-(3,4-dimethoxy-phenyl)-ethanone. To a 0° C. solution of 3,4-dimethoxyacetophenone (5.00 g, 27.8 mmol) in diethyl ether (200 mL) and CHCl3 (30 mL) was added, dropwise over 1.5 h, a solution of Br2 (1.45 mL, 27.8 mmol) in CHCl3 (30 mL). Once the addition was complete, the mixture was stirred for 1 h at 0° C., and then was allowed to warm to rt. The reaction mixture was concentrated and the residue chromatographed (CH2Cl2/hexanes) to give 5.23 g (73percent) of the ketone as a pale yellow solid. 1H NMR (DMSO-d6): 7.68 (dd, J=2.0, 8.4, 1H), 7.47 (d, J=2.0, 1H), 7.08 (d, J=8.5, 1H), 4.85 (s, 2H), 3.85 (s, 3H), 3.81 (s, 3H).
70% With bromine In chloroform at 20℃; for 3 h; To a stirred solution of 1-(3,4-Dimethoxy-phenyl)-ethanone (7) (20 g, 0.111 mol) in chloroform (200 mL) at RT added bromine solution (18.8 g, 0.111 mol) in chloroform 90 mL) over 1 h, reaction maintained at RT for 2 h, after completion of reaction by TLC, the reaction mixture quenched in to saturated sodium bicarbonate solution (300 mL) and extracted with chloroform (2 X 150 mL), organic layers combined and washed with DM water (300 mL) and dried over sodium sulfate and concentrated, co distilled with hexane (2 X 100 mL), charged methanol (50 mL) and stirred for 10 min, filtered solid (8) 20 g (70percent); mp 79-81° C; IR (KBr, Cm-1): 3570, 2779, 1684, 1266; Mass for C10H11BrO3 [M+1] 259.0; 1H NMR (400MHz, DMSO) (δ ppm): 3.84 (3H, s), 3.88 (3H, s), 4.21 (2H, s), 7.07 (1H, d, J = 8.4 Hz), 7.43 (1H, s), 7.71 (1H, dd, J1 = 1.46 Hz, J2 = 1.48 Hz); 13C NMR (100 MHz, DMSO) (δ ppm); 33.87, 55.91, 56.16, 111.1, 111.2, 124.1, 127.0, 149.0, 153.9, 190.5.
63.4% With copper(I) bromide In chloroform; ethyl acetate at 20 - 65℃; for 16 h; Compound 2(27.78 mmol, 5.00 g, 1 eq) was dissolved in 90 mL of chloroform / ethyl acetate (1: 1 by volume)In the mixed solution,Copper bromide (55.56 mmol, 12.41 g, 2 eq) was added with stirring at room temperature,Heated to 65 reflux 16 h,TLC monitors the progress of the reaction.After the reaction (the reaction liquid is blue-black,The bottom of a large number of white solid precipitation),Cooling continue stirring 0.5 h,Filter, add appropriate amount of methylene chloride to the residue to continue filtration,The combined filtrates,Dried to 6.21 g of crude product (blue black solid),The crude product was isolated and purified by silica gel column chromatography (200-300 mesh) (ethyl acetate-petroleum 0: 100 →2: 98 → 5: 95 → 10: 80 → 20: 80 → 30: 70)Finally, compound 3 (4.53 g) was obtained,Yellow-brown solid,Yield 63.4percent.
52.3% With pyridinium hydrobromide perbromide In ethanol; chloroform at 50℃; for 16 h; Step 12-bromo-1 -(3,4-dimethoxyphenyl)eth3,4-dimethoxyacetophenone (1 .00 g, 5.55 mmol) was dissolved in a 1 :1 mixture of ethanol and chloroform (60 ml_). Pyridinium tribromide (4.46 g, 13.9 mmol) was added and the mixture was stirred at 50°C for 16 h. The reaction was cooled to RT and solvents removed in vacuo to give a sticky orange solid, which was then dissolved in H20 (30 ml_), and organics extracted with EtOAc (3 x 20 mL) and washed with H20 (2 x 20 mL) and brine (20 mL). The organics were dried (MgS04), filtered and concentrated in vacuo to give an orange oil containing a mixture of mono- and di-bromated species (approx 1 :5 to 1 ratio). Flash chromatography (DCM isocratic) afforded the title compound as an off-white solid (752 mg, 2.90 mmol. 52.3percent). Spectroscopic data was consistent with that previously reported. Mpt: 62 °C [Lit. 67-70 °C]; Rf = 0.12 (DCM); IR (vmax/cm-\\ thin film): 2940 (C-H stretch), 1679 (C=0 stretch), 1585, 1512, 1465, 1418 (Aromatic C=C stretch), 1241 (C-O-C stretch); 1H NMR (500 MHz, CDCI3): δΗ = 3.93 (s, 3H, 9-H), 3.95 (s, 3H, 10-H), 4.40 (s, 2H, 1 -H), 6.90 (d, J = 8.4 Hz, 1 H, 5-H), 7.53 (d, J = 2.1 Hz, 1 H, 8-H), 7.60 (dd, J = 8.4, 2.1 Hz, 1 H, 4-H); 13C NMR (125 MHz, CDCI3): 5C = 30.5 (C-1 ), 56.1 (C-9), 56.2 (C-10), 1 10.2 (C-5), 1 10.9 (C-8), 123.9 (C-4), 127.1 (C- 3), 149.4 (C-7), 154.1 (C-6), 190.2 (C-2); LRMS m/z (El+): 260 [M(81Br)]+, 258 [M(79Br)]+, 165 [M-CH2Br]+; HRMS m/z (El+): Found 257.98872 [M(79Br)]+; Ci0HnO3Br requires 257.98861 .
49% With bromine In chloroform at 20℃; 3,4-Dimethoxyacetophenone (10 g, 55 mmol) in CHCl3 (100 mL) was stirred in a round-bottom flask, while Br2 (10.6 g, 66 mmol) was added drop-wise over 1 h; the mixture was then stirred then for 16 h at r.t. The solvent was then removed in vacuo to give an oil; addition of EtOH (40 mL) and cooling to -15 °C gave a cream-white precipitate that was filtered off, washed with EtOH (2 9 20 mL), and dried in vacuo. Yield = 7.0 g (49 percent). 1H NMR (300 MHz, CDCl3): δH = 3.95, 3.97 (OCH3, s, 3H each), 4.42 (CH2Br, s, 2H), 6.92 (Ar–H, d,1H, 3JHH = 8.7), 7.56 (Ar–H, s,1H),7.62(Ar–H, d, 1H, 3JHH = 8.4). 13C{1H} NMR (75 MHz, CDCl3): δC = 30.5 (CH2Br), 56.1, 56.2 (OCH3), 110.2, 110.9, 123.9 (CAr–H), 127.1 (CArC=O), 149.4, 154.1 (CAr–OCH3), 190.1 (C=O). ESI/MS+: 283 [M + Na]+. Anal. Calcd (Found) for C10H11O3Br: C, 46.36 (46.37); H, 4.28 (4.25).
71% With bromine In chloroform Preparation example 64
Synthesis of (E)-N-[2-(3,4-dimethoxyphenyl)-2-oxoethyl]-N-methyl-3-(3-pyridyl)-2-propenamide (compound 155)
250 mL of ether and 100 mL of chloroform were added to 14.65 g (81 mmol) of 3',4'-dimethoxyacetophenone and the mixture was stirred while cooling on ice.
4.1 mL of bromine was dissolved in 22 mL of chloroform, and added dropwise to the reaction mixture over 1 h.
After stirring the reaction mixture for 1 h at room temperature, the reaction mixture was washed with water, aqueous saturated sodium bicarbonate, and water in that order.
The organic phase was dried over magnesium sulfate and the solvent was then removed by vacuum evaporation.
The residue was purified by silica gel column chromatography (dichloromethane: ethyl acetate = 30:1) to obtain 14.90 g (71percent) of 2-bromo-1-(3,4-dimethoxyphenyl)ethanone.
1H-NMR (CDCl3)δ: 3.95 (3H, s), 3.97 (3H, s), 4.41 (2H, s), 6.91 (1H, d, J=8Hz), 7.55 (1H, d, J=2Hz), 7.62 (1H, dd, J=8Hz, 2Hz)

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YieldReaction ConditionsOperation in experiment
87.9% With nitric acid; sodium nitrite In water at 5 - 10℃; for 3 - 5 h; (1)
Step of nitration:
3,4-Dimethoxyacetophenone (1500 g) was dissolved in 17percent nitric acid (1400 g) at 5 to 10°C to prepare a solution which was then slowly added dropwise to a mixed solution composed of 67percent nitric acid (8430 g) and sodium nitrite (18 g) at 5 to 10°C over a period of 2 to 3 hr.
After the completion of the dropwise addition, the reaction solution was stirred at 5 to 10°C for 1 to 2 hr.
Cold water (7.5 L) was added thereto, and the mixture was stirred for 30 min.
The reaction solution was then filtered and was washed with water (30 L).
The filtered product was added to water (7.5 L), and the mixture was neutralized with an aqueous sodium bicarbonate solution, was then filtered, and was washed with water (7 L).
The filtered product was dried under the reduced pressure to give 3,4-dimethoxy-6-nitroacetophenone (2164 g, yield 87.9percent).
1H-NMR (400 MHz, CDCl3/ppm); δ 2.50 (s, 3H), 3.97 (s, 3H), 3.99 (s, 3H), 6.76 (s, 1H), 7.62 (s, 1H)
86% at 60℃; for 3.5 h; A mixture of 1-(3,4-dimethoxyphenyl)ethan-1-one 11 (180 g, 1.0 mol), HOAc (1.5 L) was stirred and heated to 60°C. When the solid dissolved, 65percent HNO3 (110 mL, 1.5 mol) was added over 30 min and the mixture was stirred for another 3 h to give a yellow solution. The reaction mixture was poured slowly into ice-water (5 L) while stirring constantly. The yellow solid formed was filtered off and washed with cold water (600 mL × 2), dried at 60°C for 4 h to give crude product 12 (210 g). The crude 12 (210 g) was stirred and heated with EtOAc : petroleum ether= 1:1 (v:v) (800 mL) at reflux for 2 h then cooled to room temperature, the resulting solid was filtered off and washed with EtOAc : petroleum ether = 1:1 (v:v) (100 mL × 2), dried at 50°C for 4 h to afford 12(193.7 g, 86percent) as a yellow solid; mp 131.3−133.1° C (Lit.10 130−132°C). 1H NMR (400 MHz,DMSO-d6): δ 2.52 (s, 3H), 3.90 (s, 3H), 3.93(s, 3H), 7.23 (s, 1H), 7.64 (s, 1H). MS (ESI): m/z = 226.1 [M+ H]+, 473.2 [2M + Na]+.
67% at 0℃; for 4 h; Inert atmosphere 1-(3, 4-dimethoxyphenyl)ethan-1-one (10 g) was added to acetic anhydride (30 mL). After the solution was cooled to 0 °C, a mixture of nitric acid (200 mL) and acetic anhydride (10 mL) were added dropwise. Upon completion of the addition, the reaction solution was stirred for 4 hours, poured into 1 L of ice water, filtered, washed with water and dried to obtain 1-(4,5-dimethoxy-2-nitrophenyl)ethan-1-one (8 g, 67percent).
60% With nitric acid In diethyl ether at 0℃; for 5 h; General procedure: To a solution of 3,4-di(1H,1H,2H,2H,3H,3H-perfluoroheptyloxy)acetophenone (2.14 g, 3.18 mmol) in diethyl ether (10 mL), HNO3 (15 mL) was carefully added dropwise at 0 °C. The solution was subsequently stirred at 0 °C for 5 h. The solution was added to ice water (100 mL) and the solution was extracted with ethyl acetate (40 mL x 2). The organic layer was washed with 5percent NaHCO3 (50 mL x 3) and dried over MgSO4. After concentrating the solution using a rotary evaporator, the residue was purified by recrystallization with ethanol to yield 1.38 g (1.92 mmol, 60percent) of 4g as yellow needle crystals.
50.7% for 2 h; Cooling with ice 3,4-dimethoxyacetophenone (15 g; 83.2 mmol) was added in small amounts to well stirred, ice-cooled nitric acid (sp gr 1.42; 90 ml) over a period of 1 hr. The final mixture was stirred for one further hour and then poured onto 400 g of crushed ice. When the ice had melted the resulting yellow solid was filtered off, air-dried and recrystallized from ethanol (9.5 g; 50.7percent yield).

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