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Product Details of [ 480-66-0 ]

CAS No. :480-66-0 MDL No. :MFCD00002287
Formula : C8H8O4 Boiling Point : -
Linear Structure Formula :- InChI Key :XLEYFDVVXLMULC-UHFFFAOYSA-N
M.W : 168.15 Pubchem ID :68073
Synonyms :
2,4,6-trihydroxyacetophenone;1-(2,4,6-Trihydroxyphenyl)ethanone;THAP Monohydrate

Calculated chemistry of [ 480-66-0 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.12
Num. rotatable bonds : 1
Num. H-bond acceptors : 4.0
Num. H-bond donors : 3.0
Molar Refractivity : 42.71
TPSA : 77.76 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.55 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.74
Log Po/w (XLOGP3) : 1.09
Log Po/w (WLOGP) : 1.01
Log Po/w (MLOGP) : -0.07
Log Po/w (SILICOS-IT) : 0.72
Consensus Log Po/w : 0.7

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.87
Solubility : 2.25 mg/ml ; 0.0134 mol/l
Class : Very soluble
Log S (Ali) : -2.32
Solubility : 0.814 mg/ml ; 0.00484 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.0
Solubility : 16.7 mg/ml ; 0.0995 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.1

Safety of [ 480-66-0 ]

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 [ 480-66-0 ]

* 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 [ 480-66-0 ]
  • Downstream synthetic route of [ 480-66-0 ]

[ 480-66-0 ] Synthesis Path-Upstream   1~32

  • 1
  • [ 480-66-0 ]
  • [ 127-09-3 ]
  • [ 1013-69-0 ]
YieldReaction ConditionsOperation in experiment
47% at 180℃; for 0.666667 h; Microwave irradiation 5,7-dihydro-2-methyl-4H-chromen-4-one: A mixture of 1 -(2,4,6-trihydroxyphenyl)ethan-1-one (2.02 g, 12.0 mmcl), AcONa (0.984 g, 12.0 mmol) in Ac20 (6.0 mL) was heated at 180 °C for 40 mm in a microwave reactor. The reaction mixture was poured into water, extracted with ethyl acetate (EA) , washed with sat’d NaHCO3 and brine, dried over Na2SO4, and concentrated. The residue was treated with a solution of K2003 (4.98 g, 36 mmol) in H20 (90 mL) and refluxed for 3 h. Acidified with 3 N HCI. The precipitate was collected by vacuum filtration to afford 1 .09 g (47percent) of 5,7-dihydro-2-methyl-4H-chromen-4-one as a yellow solid. Rff 0.45 (hexanes: EA = 1: 1); LC-MS (ESI): mlz 193 [M+1]’H NMR (400 MHz, DMSO-d6) ö (ppm) 2.35 (s, 3H), 6.17 (d, J=2.0 Hz, 2H), 6.33 (d, J=2.0 Hz, 1H), 10.78 (s, IH), 12.82 (s, IH)
Reference: [1] Journal of Organic Chemistry, 2010, vol. 75, # 2, p. 353 - 358
[2] Patent: WO2016/118822, 2016, A1, . Location in patent: Page/Page column 28
  • 2
  • [ 480-66-0 ]
  • [ 108-24-7 ]
  • [ 1013-69-0 ]
Reference: [1] Proceedings - Indian Academy of Sciences, Section A, 1949, # 30, p. 107,112
[2] Journal of Organic Chemistry, 2015, vol. 80, # 3, p. 1632 - 1643
  • 3
  • [ 6217-54-5 ]
  • [ 89-84-9 ]
  • [ 1139-83-9 ]
  • [ 480-66-0 ]
  • [ 1143-70-0 ]
  • [ 118-93-4 ]
Reference: [1] Patent: US2005/282781, 2005, A1, . Location in patent: Page/Page column 10
  • 4
  • [ 6217-54-5 ]
  • [ 89-84-9 ]
  • [ 1139-83-9 ]
  • [ 480-66-0 ]
  • [ 1143-70-0 ]
  • [ 118-93-4 ]
Reference: [1] Patent: US2005/282781, 2005, A1, . Location in patent: Page/Page column 10
  • 5
  • [ 480-66-0 ]
  • [ 548-83-4 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1984, # 7, p. 1511 - 1513
  • 6
  • [ 480-66-0 ]
  • [ 855-97-0 ]
Reference: [1] Australian Journal of Chemistry, 2012, vol. 65, # 10, p. 1377 - 1383,7
[2] Asian Journal of Chemistry, 2016, vol. 28, # 5, p. 1139 - 1143
[3] Synthesis (Germany), 2018, vol. 50, # 8, p. 1610 - 1620
  • 7
  • [ 480-66-0 ]
  • [ 53350-26-8 ]
Reference: [1] Journal of Heterocyclic Chemistry, 2002, vol. 39, # 6, p. 1251 - 1258
[2] Canadian Journal of Research, 1932, vol. 7, p. 285,289
[3] Canadian Journal of Research, 1932, vol. 7, p. 285,289
[4] Synthesis (Germany), 2018, vol. 50, # 8, p. 1610 - 1620
  • 8
  • [ 480-66-0 ]
  • [ 77-78-1 ]
  • [ 90-24-4 ]
YieldReaction ConditionsOperation in experiment
100% With potassium carbonate In acetone for 3 h; Reflux To a refluxing solution of 2,4,6-trihydroacetophenone-monohydrate (10 g, 53.7 mmol) and K2CO3 (15 g, 108.7 mmol) in acetone (150 mL), (CH3)2SO4 was added at three hour intervals (3 x 3.5 mL, 40.0 mmol). The solution was filtered and the solvent was evaporated to afford 2,4-dimethoxy-6-hydroxyacetophenone as a yellow solid (98percent).
99% With potassium carbonate In acetone at 0 - 20℃; Inert atmosphere Example 14
synthesis of 1-(2-hydroxy-4,6-dimethoxyphenyl)ethanone (11)
To a solution of commercial 2',4',6'-trihydroxyacetophenone dihydrate (15.0 g, 80.57 mmol, 1eq) in acetone (170 mL), potassium carbonate (23.4 g, 169.20 mmol, 2.1 eq) and dimethylsulfate (15.6 mL, 165.17 mmol, 2.05 eq) were added under argon at 0°C.
After vigorous stirring at room temperature for 17h, the resulting mixture was filtered and the filtrate concentrated in vacuo.
The resulting product 5 was recristallized from ethyl acetate / heptanes (3/97) to give 15.80 g (99percent) of a pale yellow solid.
Molecular Weight: 196.20 (C10H12O4).
1H-NMR δ (CDCl3, 300 MHz) ppm (J in Hz): 2.61 (s, 3H, CH3CO), 3.82 (s, 3H, MeO), 3.85 (s, 3H, MeO), 5.91 (d, 1H, J=2.4, H- 3'), 6.05 (d, 1H, J=2.4, H-5'), 14.03 (s, 1H, OH).
99% With potassium carbonate In acetone 2,4,6-trihydroxy-acetophenone (2) and the reaction wasdissolved in a dimethyl sulfate to potassium carbonate in acetone to synthesize4,6-dimethoxy-2-hydroxy acetophenone (3)
95.8% With potassium carbonate In acetone at 10 - 15℃; A mixtureof phloroacetophenone (1) (300 g, 1.78 mol), acetone (1.5 L)and potassium carbonate (739.2 g, 5.35 mol) was chargedunder stirring at room temperature. Dimethyl sulphate (494.9g, 3.92 mol) was charged drop wise with the help of the additionfunnel at 10-15 °C for 3 h. TLC (20 percent EtOAc in hexane)showed no traces of starting material but observed traces oftrimethoxyacetophenone. After completion of the reaction, thereaction mixture was poured into ice cold water and stirredfor 3 h. A crude solid material was obtained on filtration andwashed with cold water and drained thoroughly. The yieldwas 84 percent with a purity of 95.8 percent obtained.
94% With potassium carbonate In acetone for 2 h; Reflux A mixture of 2,4,6-trihydroxyacetophenone (1) (1.0 g, 5.95 mmol) anhydrous K2CO3 (1.64 g, 11.88 mmol) and (CH3)2SO4 (1.08 mL, 11.22 mmol) was stirred and refluxed in acetone (60 mL) for 2 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was evaporated and the residue subjected to silica gel column chromatography with PE/AcOEt 2:1 as an eluent to afford white solids 1.1 g, yield: 94percent. m.p. 77-79 °C (Lit.1: 79~80°C ).
93.5%
Stage #1: With potassium carbonate In acetone at 25℃; for 0.5 h;
Stage #2: at 25℃;
To a solution of 1-(2,4,6-trihydroxyphenyl)ethanone (11.16 g, 0.06 mol) in dry acetone (150 mL), potassium carbonate (24.84 g, 0.18 mol) was added and stirred for 30 min at room temperature. Then dimethyl sulphate (12 mL, 0.12 mol) was added drop-wise, the reaction solution was stirred for 4-5 h at room temperature and monitored by thin-layer chromatograph (TLC). Poured the reaction solution to ice-water (1000 mL) and the precipitate was filtered, washed with water, dried to afford 1 (11.0 g) as white solid in 93.5percent yield. 1H NMR (400 MHz, DMSO‑d6) δ: 13.79 (s, 1H, OH), 6.11 (d, 1H, J = 2.3 Hz), 6.08 (d, 1H, J = 2.3 Hz), 3.86 (s, 1H), 3.81 (s, 1H), 2.55 (s, 1H).
13C NMR (100 MHz, DMSO‑d6) δ: 203.2, 166.7, 166.4, 163.2, 105.9, 94.1, 91.2, 56.5, 56.1, 33.1.
87% With potassium carbonate In acetoneReflux (1 g, 5.95 mmol) was dissolved in 30 ml of acetone followed by the addition of potassium carbonate (4.11 g, 5 eq.), And dimethylsulfate (4 eq) was added dropwise. The suspension was refluxed for 5 to 8 hours. After the reaction, the reaction mixture was cooled to room temperature, filtered and washed with acetone. The filtrate was evaporated under reduced pressure to give intermediate 5a (2-hydroxy-4,6-dimethoxyacetophenone) , 6a (2-hydroxy-4,6-diethoxyacetophenone) (5a, 1.01 g, yield 87percent; 6a, 1.15 g, 79percent yield); intermediate 5a, 6a, (4-hydroxy-5,7-dimethoxycoumarin), 6b (4-hydroxy-5,7-diethoxy coumarin) obtained by Method B of Method 9, (44 mg), 6b (50 mg) were each obtained by the method A of Example 9 to obtain the compound of the formula (5b, 1.00 g, yield 93percent; 6b, 1.07 g, yield 91percent 6,6 (Derivative 5, 60 mg, yield 74percent; derivative 6,63 mg, 64percent); nitration was carried out using Intermediate 6b (500 mg, 2 mmol) (see reaction of compound 2 (68 mg, yield 85percent) was obtained from Intermediate 6c (59 mg, 0.2 mmol) followed by Method A of Example 9 to give the intermediate 6c (484 mg, yield 82percent
84.2% With potassium carbonate In acetone for 5 h; Reflux 4.1.5
1-(2-Hydroxy-4,6-dimethoxyphenyl)ethanone (16)
To a mixture of 1-(2,4,6-trihydroxyphenyl)ethanone 15 (4.5 g, 24.2 mmol) and anhydrous K2CO3 (8.29 g, 55.6 mmol) in acetone (90 mL), Me2SO4 (6.84 mL, 72.5 mmol) was added dropwise with stirring.
The resulting mixture was refluxed for 5 h and then filtered and concentrated under reduced pressure.
The residue was purified on a silica gel chromatography using CH2Cl2 as eluent, obtaining compound 16; 84.2percent yield; white solid; mp 78-79 °C (lit.
38
79-80 °C).
84% With potassium carbonate In acetone at 0 - 20℃; for 3 h; Inert atmosphere To a stirred solution of ketone 1 (1.18 g, 10 mmol) and K2CO3 (3.45 g 25 mmol) in acetone (20 mL), (CH3)2SO4 (2.37 mL, 25 mmol) was added dropwise at 0 °C. After stirring at room temperature for 3 h, the solvent was then removed under reduced pressure. The residue was dissolved in water (30 mL) and the solution was extracted three times with EtOAc. The combined organics were washed with water and brine, then dried over anhydrous MgSO4 and concentrated in vacuo to give compound 11 (1.65 g, 84percent). 1H NMR (500 MHz, CDCl3) δ 14.03 (s, 1H), 6.08 (d, J = 2.4 Hz, 1H), 5.94 (d, J = 2.4 Hz, 1H), 3.87 (s, 3H), 3.84 (s, 3H), 2.63 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 203.19, 167.58, 166.09, 162.91, 105.97, 93.45, 90.71, 55.55, 32.96; ESIMS: m/z = 197.2 [M+H]+.
82% With potassium carbonate In acetone at 20℃; 1 -(2,4,6- trihydroxyphenyl)ethanone, 4, (16.8 g, 0.10 mol), anhydrous potassium carbonate (41.50 g, 0.30 mol) and anhydrous acetone (168 mL) were combined and stirred at room temperature after which dimethyl sulfate (26.9 g, 0.21 mol) was slowly added. Once the addition was complete, the reaction was stirred for 1 hour. The pH of the solution was adjusted to neutral using 2N HCl. The resulting yellow solid was collected by filtration and washed with water then dried to afford 16 g (82percent yield) of the desired product as a white solid. M.p. 76-78 0C.
82% With potassium carbonate In acetone for 0.333333 h; Reflux; Inert atmosphere K2CO3 (7.23 g, 52.32 mmol) and Me2SO4 (2.48 mL, 26.16 mmol) were added to a solution of 2′,4′,6′-trihydroxyacetophenone (1, 2.00 g, 11.89 mmol) in acetone (50 mL). The reaction mixture was refluxed for 20 min under nitrogen atmosphere. After that, K2CO3 was filtered off, the acetone evaporated, and the residue recrystallized in EtOH affording the 2′-hydroxy-4′,6′-dimethoxyacetophenonein good yield (82percent, 1.91 g).
82.5% With potassium carbonate In acetone at 20℃; This compound was prepared from a mixture of 1 (17.85 mmol, 3 g), K2CO3 (43.47 mmol, 6 g), Me2SO4 (19.67 mmol, 3.85 g), and 50 ml acetone, which was stirred at RT for 5–6 h, and then, the mixture was poured into water (300 ml). The precipitated solid was filtered, washed with water, and crystallized from 95 percent ethanol to give 2 as white powder, yield: 82.5 percent; IR (KBr) νmax 2,960 (OH),1,620 (C=O) cm-1; 1H NMR (DMSO-d6, 400 MHz): δ = 14.15 (1H, s, OH), 6.36 (1H, d, J = 2.5 Hz, H-3), 5.97(1H, d, J = 2.7 Hz, H-5), 3.89 (3H, s, OCH3-4), 3.83 (3H,s, OCH3-6), 2.7 (3H, s, COCH3). 13C NMR (DMSO-d6,100 MHz): δ = 203.1 (C, C=O), 167.6 (C, C-4), 166.1(C,C-6), 162.9 (C, C-2), 106.0 (C, C-1), 92.9 (CH, C-3), 90.1(CH, C-5), 55.4 (2CH3, OCH3), 32.1(CH3, COCH3); ESI–MS: m/z 197.09 [M+H]+. Anal. Calcd. for C10H12O41 96.07: C, 61.22; H, 6.16. Found: C, 61.27; H, 6.19.
81.36% With potassium carbonate In acetone at 50℃; for 6 h; Anhydrous operation, 5 g of Intermediate 6 (26.85 mmol) was put in 80 ml of acetone, and 7.5 g of potassium carbonate was added(54.35 mmol) and 5.25 ml of dimethyl sulfate (20 mmol) were added, and the reaction solution was heated to 50 ° C, After the reaction was completed for 6 hours, the excess acetone was removed by distillation under reduced pressure, Purification by column chromatography gave a white solid in a yield of 81.36percent.
78% With potassium carbonate In acetone for 20 h; Reflux The 9g compound (1) is dissolved in 30 ml of acetone, is added under stirring 14g potassium carbonate, then using the constant voltage dropping funnel slowly add sulfuric acid dimethyl ester 15g, reflux stirring 20h, cooling to room temperature, adding ice water precipitating a large amount of white solid, filtered, methanol recrystallization to obtain 7.5g white solid (2), yield 78percent. Compound mp: 74.4-75.1 °C.
78% With potassium carbonate In acetone for 20 h; Reflux The compound 1 (9g ) dissolved in 30ml of acetone, 14g of potassium carbonate was added under stirring, then added slowly with constant pressure dropping funnel dimethyl sulfate 15g, was stirred at reflux for 20h, cooled to at room temperature, ice water was added to precipitate large amount of white solid was suction filtered, and recrystallized from methanol to give a white solid 7. 5g (2), a yield of 78percent. Compound mp 74. 4-75. 1 ° C. The product structure was confirmed by IR, NMR and MS analysis
75% With potassium carbonate In acetone at 20℃; for 4 h; The 2,4,6-trihydroxyacetophenone monohydrate (3.72g, 20mmol) added to acetone (60 ml), then adding potassium carbonate (6.06g, 40mmol)with stirring, undissolved, then slowly dropping dimethyl sulfate (4 ml, 42mmol), after completion of dropwise addition the reaction was stirred at the room temperature 4 hours and degree of reaction was monitored by TLC monitoring. The end of the to be reacted, filtering off the solid insoluble materials, ten slowly adding water (100 ml), repeated oscillation, allowed to stand for half an for white solid precipitation. Filtering, drying to obtain the white solid (3.0g), yield 75percent.
74% With potassium carbonate In acetone for 5 h; Reflux To a solution of 2’,4’,6’-trihydroxyacetophenone (3) (10.0 g, 59.5 mmol) in acetone (350 mL)was added K2CO3 (16.45 g, 119 mmol, 2.0 equiv) while stirring with a KPG stirrer at room temperature. Dimethyl sulfate (14.15 g, 112.2 mmol, 10.6 mL) was added dropwise to the suspension under vigorous stirring and then the reaction mixture was refluxed for 5 h. Then the reaction mixture was allowed to cool down and was stirred overnight. Afterwards, the reaction mixture was filtered, the solvent was evaporated under vacuum and the residue was recrystallized from methanol (15 mL). The crystals were filtered, washed with water to yield 8.65 g (44.1 mmol, 74percent) off-white solid; mp 74-75 °C [Lit. 73-76 °C]. Spectroscopic data is in accordance with the literature.
54% With potassium carbonate In acetone for 10 h; Reflux
A mixture of 1-(2,4,6-trihydroxyphenyl)ethan-1-one (2.50 g, 15 mmol), (CH3)2SO4 (2.85 mL, 30 mmol) and anhydrous K2CO3 (4.56 g, 33 mmol) in dry acetone (60 mL) was refluxed for 10 h.
The reaction mixture was concentrated and poured on to ice-water (100 mL).
The resulting precipitate was filtered off and washed with cold water.
The obtained residue was purified by silica gel column chromatography with hexane: ethyl acetate (95: 5) as eluent.
White solid, Yield: 54percent, M.P: 78-80 °C; 1H NMR (CDCl3, 400 MHz, ppm) δ: 14.03 (s, 1H,-OH), 6.06-6.05 (d, J = 2.20 Hz, 1H, Ar-H), 5.93-5.92 (d, J = 2.20 Hz, 1H, Ar-H), 3.86, 3.82 (s, each 3H, 2 * -OCH3), 2.61 (s, 3H, -COCH3); 13C NMR (CDCl3, 100 MHz, ppm) δ: 203.17 (-C=O); 167.56; 166.06; 162.88; 105.97; 93.43; 90.72; 55.53 (-OCH3); 50.86 (-OCH3); 32.91 (-CH3).

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[5] Patent: KR2015/49695, 2015, A, . Location in patent: Paragraph 0063-0072
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[15] Synthesis (Germany), 2012, vol. 44, # 14, p. 2217 - 2224
[16] Green Chemistry, 2013, vol. 15, # 11, p. 3165 - 3169
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  • 9
  • [ 480-66-0 ]
  • [ 90-24-4 ]
YieldReaction ConditionsOperation in experiment
94.4% With potassium carbonate; dimethyl sulfate In acetone Production Example 7
To 50.1 g of 2',4',6'-trihydroxyacetophenone and 123.5 g of anhydrous potassium carbonate was added 500 ml of anhydrous acetone, and the mixture was stirred at room temperature for 30 minutes.
Then, 78.9 g of dimethyl sulfate was added to the reaction mixture, and the mixture was stirred at room temperature for 1.5 hours to effect a reaction.
After the reaction, the reaction mixture was neutralized with dilute hydrochloric acid, extracted with diethyl ether and filtered, and the solvent was removed from the filtrate by distillation.
The obtained residue was recrystallized from n-hexane to obtain 55.2 g (yield=94.4percent) of 2'-hydroxy-4',6'-dimethoxyacetophenone in the form of a colorless prism.
Melting point: 77° to 78° C.
Infrared absorption spectrum νmaxKBr cm-1: 1622, 1596, 1574, 1460, 1440, 1424, 1368, 1272, 1222, 1206, 1156, 1110, 1080, 894, 834,
596.
Proton nuclear magnetic resonance (δ ppm in CDCl3): 2.61 (3H, s), 3.82 (3H, s), 3.85 (3H, s), 5.92 (1H, d, J=2.4 Hz), 6.05 (1H, d, J=2.4 Hz), 14.03 (1H, s, disappeared by addition of D2 O).
Reference: [1] Patent: US5106871, 1992, A,
[2] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 19, p. 4672 - 4677
  • 10
  • [ 480-66-0 ]
  • [ 616-38-6 ]
  • [ 90-24-4 ]
YieldReaction ConditionsOperation in experiment
69% With potassium carbonate In dimethyl sulfoxide at 120℃; Compound 4 (2.5 g, 0.015 mol), K2CO3 (1.7 g, 0.01 mol), and DMC (7.5 mL, 0.09 mol) in DMSO (20 mL) were heated at 120 °C until TLC showed that compound 4 had disappeared. Then the mixture was cooled to room temperature and H2O (30 mL) was added. The reaction mixture was neutralised to pH 3–4 with 10percent aqueous HCl and the precipitate was filtered and recrystallised from methanol to give compound 3 (2.0 g), yield 69percent, white crystals, m.p. 81–82 °C (lit.22 80–81 °C) 1H NMR (500 MHz, DMSO-d6) (δ, ppm): 2.60 (s, 3H,COCH3), 3.81 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 5.92 (s, 1H, ArH), 6.05 (s, 1H, ArH), 14.02 (s, 1H, OH). IR νmax (KBr/cm−1): 3461 (OH), 1619 (C=O).
Reference: [1] Journal of Chemical Research, 2014, vol. 38, # 11, p. 686 - 689
  • 11
  • [ 480-66-0 ]
  • [ 74-88-4 ]
  • [ 90-24-4 ]
YieldReaction ConditionsOperation in experiment
36% With potassium carbonate In acetone for 24 h; Reflux; Darkness 4.1.1
1-(2-Hydroxy-4,6-dimethoxyphenyl)ethan-1-one 21
2,4,6-Trihydroxyacetophenone (2 g, 10.7 mmol), methyl iodide (2.70 mL, 42.9 mmol) and K2CO3 (2.96 g, 21.4 mmol) were dissolved in 50 mL of acetone.
The mixture was heated to reflux for 24 h in the dark.
The reaction mixture was filtered under vacuum, and the filtrate was evaporated under reduced pressure.
The crude product was purified by flash chromatography using cyclohexane/ethyl acetate 95:5 as eluting system; 1.13 g of title compound 21 were obtained. Yield: 36percent. 1H NMR (CDCl3) δ: 6.05 (d, J = 2.4 Hz, 1H, CH arom.); 5.92 (d, J = 2.4 Hz, 1H, CH arom.); 3.85 (s, 3H, OCH3); 3.81 (s, 3H, OCH3); 2.60 (s, 3H, CH3) ppm.
1.2 g With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 48 h; Heating 2, 4, 6-tri-hydroxy acetophenone 2g (12mmol), added to the 15mlDMF in, then adding CH 3 I1.72g (12.1mmol), K 2 CO 3 5 g. Stir at room temperature reaction 48h, is poured into the reaction liquid to the ice water, stirring 1h, then filter. Drying the obtained solid, recrystallized with ethanol, to obtain 2-hydroxy -4,6-di-methoxy acetophenone 1.2 g.
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 18, p. 2271 - 2284
[2] Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1346 - 1351
[3] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 1, p. 50 - 64
[4] Patent: CN105669625, 2016, A, . Location in patent: Paragraph 0172
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Reference: [1] Patent: US4024272, 1977, A,
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Reference: [1] Organic and Biomolecular Chemistry, 2017, vol. 15, # 23, p. 5025 - 5032
[2] Journal of Chemical Research, 2012, vol. 36, # 3, p. 121 - 122
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  • [ 75-18-3 ]
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Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 15, p. 3464 - 3467
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  • [ 333-27-7 ]
  • [ 90-24-4 ]
Reference: [1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 11, p. 3061 - 3068
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  • [ 23121-32-6 ]
Reference: [1] Journal of Natural Products, 2008, vol. 71, # 7, p. 1237 - 1241
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  • [ 7507-89-3 ]
Reference: [1] Journal of Natural Products, 2003, vol. 66, # 8, p. 1144 - 1146
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Reference: [1] Tetrahedron Letters, 1985, vol. 26, # 39, p. 4807 - 4810
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Reference: [1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1987, vol. 26, p. 57 - 58
[2] Journal of the Indian Chemical Society, 1987, vol. 64, # 4, p. 253 - 254
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Reference: [1] European Journal of Medicinal Chemistry, 2010, vol. 45, # 9, p. 4258 - 4269
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Reference: [1] Chemische Berichte, 1925, vol. 58, p. 1697
[2] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 4, p. 525 - 528
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Reference: [1] Chemische Berichte, 1925, vol. 58, p. 1697
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Reference: [1] Tetrahedron, 2014, vol. 70, # 26, p. 3963 - 3970
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  • [ 19309-14-9 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 14, p. 2986 - 2992
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  • [ 16600-92-3 ]
Reference: [1] Monatshefte fuer Chemie, 1982, vol. 113, p. 73 - 80
  • 26
  • [ 480-66-0 ]
  • [ 100-44-7 ]
  • [ 18065-05-9 ]
YieldReaction ConditionsOperation in experiment
75% at 90℃; for 3 h; To a solution of 1-(2,4,6-trihydroxyphenyl)ethanone (1) (60 g, 0.36 mol) in HMPA (300 mL) was added K2CO3 (148 g, 1.07 mol) and BnCl (86.3 mL, 0.75 mol), and the suspension was stirred at 90 °C for 3 h. The solid was filtered, and the filtrate was poured into ice-water. The pH of the solution was adjusted to 2 by adding diluted hydrochloric acid. The resulting solid was filtered and recrystallized in CH2Cl2/MeOH to give 1-(2,4-bis(benzyloxy)-6-hydroxyphenyl)ethanone (2). Yield: 75percent; 1H NMR (CDCl3, 300 MHz) δ: 2.56 (3H, s) 5.06 (4H, s), 6.11 (1H, s), 6.17 (1H, s), 7.41 (10H, m), 14.04 (1H, s).
66.5% With potassium carbonate In N,N,N,N,N,N-hexamethylphosphoric triamide at 90 - 93℃; for 1.5 h; [0165] A mixture of 2',4',6'-trihydroxyacetophenone (20 g, 0.12 mol, dried in the oven at 140° C.) and anhydrous potassium carbonate (50 g, 0.36 mol) in hexamnethylphosphoramide (160 mL) was treated with benzyl chloride (30 mL, 0.26 mol), and the suspension heated at 90-93° C., under an argon atmosphere, for 1.5 h. The mixture was then cooled and filtered. The filtrate was added to 300 mL ice-cold water and acidified to pH 4 with 6N hydrochloric acid. The resulting suspension was heated to 70° C. for 1 h, and then cooled at 4° C. for 16 h. The deposited sticky solid was filtered off and washed with water. This solid was air-dried, and recrystallized from boiling methanol/acetone (2:1). Cooling the solution afforded the product 8 as off-white crystals (27.55 g, 66.5percent yield). 1H NMR (300 MHz, CDCl3): δ2.56 (s, 3H, CH3), 5.06 (s, 4H, CH2), 6.10 and 6.16 (2s, 2H, 3',5'-Ar-H), 7.40 (m, 10H, Ar-H), 14.01 (s, 1H, OH).
66.5% With potassium carbonate In N,N,N,N,N,N-hexamethylphosphoric triamide; water (b)
Preparation of 4',6'-bisbenzyloxy-2'-hydroxyacetophenone (8) from 2',4',6'-trihydroxyacetophenone 7:
A mixture of 2',4',6'-trihydroxyacetophenone (20 g, 0.12 mol, dried in the oven at 140° C.) and anhydrous potassium carbonate (50 g, 0.36 mol) in hexamethylphosphoramide (160 mL) was treated with benzyl chloride (30 mL, 0.26 mol), and the suspension heated at 90-93° C., under an argon atmosphere, for 1.5 h.
The mixture was then cooled and filtered.
The filtrate was added to 300 mL ice-cold water and acidified to pH 4 with 6N hydrochloric acid.
The resulting suspension was heated to 70° C. for 1 h, and then cooled at 4° C. for 16 h.
The deposited sticky solid was filtered off and washed with water.
This solid was air-dried, and recrystallized from boiling methanol/acetone (2:1).
Cooling the solution afforded the product 8 as off-white crystals (27.55 g, 66.5percent yield).
1H NMR (300 MHz, CDCl3): δ 2.56 (s, 3H, CH3), 5.06 (s, 4H, CH2), 6.10 and 6.16 (2s, 2H, 3',5'-Ar-H), 7.40 (m, 10H, Ar-H), 14.01 (s, 1H, OH).
66.5% With potassium carbonate In N,N,N,N,N,N-hexamethylphosphoric triamide at 90 - 93℃; for 1.5 h; A mixture of 2',4',6'-trihydroxyacetophenone (20 g, 0.12 mol, dried in the oven at 140° C.) and anhydrous potassium carbonate (50 g, 0.36 mol) in hexamethylphosphoramide (160 mL) was treated with benzyl chloride (30 mL, 0.26 mol), and the suspension heated at 90-93° C., under an argon atmosphere, for 1.5 h. The mixture was then cooled and filtered. The filtrate was added to 300 mL ice-cold water and acidified to pH 4 with 6N HCl. The resulting suspension was heated to 70° C. for 1 h, and then cooled at 4° C. for 16 h. The deposited sticky solid was filtered off and washed with water. This solid was air dried, and recrystallized from boiling methanol/acetone (2:1). Cooling the solution afforded the product 8 as off-white crystals (27.55 g, 66.5percent yield). 1H NMR (300 MHz, CDCl3): δ 2.56 (s, 3H, CH3), 5.06 (s, 4H, CH2), 6.10 and 6.16 (2s, 2H, 3',5'-Ar-H), 7.40 (m, 10H, Ar-H), 14.01 (s, 1H, OH).
62% With potassium carbonate In N,N-dimethyl-formamide at 0 - 70℃; Inert atmosphere To a mixture of ketone 1 (3.36 g, 20 mmol) and K2CO3 (7 g) in DMF (28 mL), benzyl chloride (4.5 mL) was slowly added at 0 °C. After stirring at 70 °C over night, the reaction mixture was diluted with water (30 mL), and the resulting mixture was extracted with EtOAc. The organic layer was washed with water and brine, then dried over anhydrous MgSO4 and concentrated in vacuo. The residue was purified by silica gel chromatography eluted with PE/EtOAc (4:1) to afford compound 2 (4.31 g, 62percent) as white solid. 1H NMR (500 MHz, CDCl3) δ 14.02 (s, 1H), 7.44 – 7.31 (m, 10H), 6.17 (d, J = 2.3 Hz, 1H), 6.10 (d, J = 2.3 Hz, 1H), 5.06 (s, 2H), 5.06 (s, 2H), 2.56 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 203.21, 167.58, 165.11, 162.01, 135.88, 135.63, 128.77, 128.74, 128.49, 128.38, 127.99, 127.66, 106.37, 94.76, 92.38, 71.13, 70.28, 33.32; ESIMS: m/z = 349.3 [M+H]+.
46%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide at 35 - 65℃; Inert atmosphere
Stage #2: at 65 - 70℃; for 3 h; Inert atmosphere
A 1 L 3-neck flask was charged with N,N-dimethylformamide (180 mL) under nitrogen, heated to 35 °C, then phloroglycinol hydrate (37.23 g, 0.20 mol) was added in one portion, followed by more DMF (120 mL). Potassium carbonate (60.8 g, 0.44 mol) was added and the mixture was heated to 65 °C. Benzyl chloride (50.6 mL, 0.44 mol) was introduced in one portion, and the mixture was heated to 70 °C for 3 h, cooled to room temperature, and filtered. The filter cake was then rinsed with methylene chloride. The combined filtrates were concentrated in vacuo and the residual orange oil was taken up in dichloromethane (400 mL), stirred for a few minutes, filtered, and the filtrate added to a pad of silica gel and eluted with dichloromethane. The filtrate volume was reduced to 150 mL, after which heptane (200 mL) was added, and the mixture was stirred for 20 min. The resultant white crystalline solid was collected by filtration, washed with heptane and air dried. The filtrate solution was loaded directly onto a silica gel column (700 mL) and eluted with 1:1 dichloromethane/heptane, then with 2:1 dichloromethane/heptane to yield additional product. The two batches were combined to afford 32.22 g (46percent) of 2,4-dibenzyloxy-6-hydroxyacetophenone 6a as a white crystalline solid: mp 103.5–105.5 °C (lit.33 103 °C); LC/MS m/z 349 [M+H]; 1H NMR (CDCl3, 400 MHz) δ 2.56 (s, 3H), 5.07 (m, 4H), 6.10 (d, J = 2.3, 1H), 6.17 (d, J = 2.3, 1H), 7.31–7.45 (m, 10H), 14.02 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 33.4, 70.4, 71.3, 92.5, 95.0, 106.6, 127.8, 128.1, 128.5, 128.6, 128.86, 128.9, 135.8, 136.1, 162.2, 165.3, 167.7, 203.3. Anal. Calcd for C22H20O4: C, 75.84; H, 5.79. Found: C, 75.88; H, 5.79.

Reference: [1] Journal of Chemical Research - Part S, 1999, # 2, p. 148 - 149
[2] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1987, vol. 26, # 1-12, p. 488 - 490
[3] Synthesis, 2010, # 16, p. 2776 - 2786
[4] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 8, p. 2864 - 2871
[5] Biochemical Pharmacology, 2014, vol. 92, # 2, p. 358 - 368
[6] Patent: US2003/229136, 2003, A1, . Location in patent: Page 18
[7] Patent: US2004/29914, 2004, A1,
[8] Patent: US2004/110790, 2004, A1, . Location in patent: Page 12
[9] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 6, p. 1441 - 1445
[10] Tetrahedron Asymmetry, 2013, vol. 24, # 7, p. 362 - 373
[11] Synthetic Communications, 1981, vol. 11, # 10, p. 853 - 858
[12] Proceedings - Indian Academy of Sciences, Section A, 1949, vol. 29, p. 1,7
[13] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1981, vol. 20, # 9, p. 770 - 772
[14] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 3, p. 826 - 832
[15] Heterocycles, 1996, vol. 43, # 2, p. 277 - 285
[16] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 20, p. 2763 - 2767
[17] Journal of Medicinal Chemistry, 2006, vol. 49, # 13, p. 3973 - 3981
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YieldReaction ConditionsOperation in experiment
95% With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6 h; 2,4,6-trihydroxyacetophenone (4.2 g, 25 mmol), bromobenzyl (9 mL,75 mmol), K2C03 (10.35 g, 75 mmol), DMF 50 ml, stirred at room temperature for 6 h, and monitored by TLC. After the reaction was completed, the reaction solution was poured into 200 mL of water, extracted three times with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (eluent: (Eluent: DCM / MeOH (v / v) = 40: 1) to give 8.26 g of a white solid, intermediate 5 in 95percent yield.
85%
Stage #1: With potassium carbonate In acetone at 65℃; for 1 h;
Stage #2: for 16 h;
The solution of 2,4,6-trihydroxyacetophenone (5 g,29.76 mmol) and anhydrous K2CO3 (15 g, 108.6 mmol) in120 mL dry acetone was refluxed at 65 °C for 1 h. Then BnBr (7.5 mL, 63.05 mmol) was added dropwise. After stirring for 16 h, the organic phase was separated. The solvent was removed, and the residue was purified by column chromatography on silica gel (petroleum ether-EtOAc, v/v, 30:1) to give 2 (8.8 g, 85percent) as white solids, mp 95-96 °C;
70%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide at 0℃; for 0.25 h; Inert atmosphere
Stage #2: at 0 - 23℃;
Step 1:
Synthesis of 1-(2,4-bis(benzyloxy)-6-hydroxyphenyl)-ethanone:
To a stirred solution of [50] (3.0 g, 16.19 mmol) in DMF, anhydrous K2CO3 (5.56 g, 40.32 mmol) was added at 0° C. under nitrogen atmosphere.
After an additional stirring at this for 15 minutes at same temperature, benzyl bromide (4.92 ml, 40.32 mmol) was added drop-wise.
The reaction temperature was allowed to increase up to 23° C. and stirring was continued for overnight.
Consumption of [50] was monitored by TLC.
After complete consumption of [50], water (50 ml) was added and organic layer was extracted with ethyl acetate (2*100 ml).
The combined organic layers were washed with water, brine and dried over sodium sulphate.
The organic layer was concentrated to afford light brown sticky material which was further purified using silica gel column chromatography using 5percent ethyl acetate/hexane as eluent to afford [51] as white powder (3.2 g, 70percent). ESIMS: 349[M+1]
69% With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 1 h; To a solution of 5 (59.6 mmol) in DMF was added K2CO3 (2.2. equiv.). After stirring for 10 min at 0° C., BnBr (2.2. equiv.) was added and the mixture stirred for 1 h at room temperature. [0081] HCl 2M was added and the mixture was poured into water and extracted with EtOAc. Organic layers were combined, washed with brine, dried over MgSO4 and concentrated. Compound 6 was purified by CC (10:1 hexane/EtOAc) in 69percent yield. Rf=0.73 (4:1 P. Ether/EtOAc); pf. 103.5-104.0° C. (Lit. [66] p.f.=108-109° C.); 1H RMN (CDCl3) δ 14.17 (s, 1H, OH-8); 7.47-7.40 (m, 20H, CH, Ph); 6.22 (d, 1H, J5,7=2.32 Hz, H-7); 6.15 (d, 1H. J5,7=2.32 Hz, H-5); 5.09 (s, CH2Ph-4); 5.08 (s, CH2Ph-6); 2.61 (s, 3H, H-1); 13C RMN (CDCl3) δ 203.2 (C-2); 167.6 (C-6 e C-8); 162.1 (C-4); 135.9 (Cq-4); 135.7 (Cq-6); 128.8; 128.7; 128.5; 128.4; 128.1; 127.7 (CH, Ph); 106.3 (C-3); 94.8 (C-7); 92.4 (C-5); 71.2 (CH2Ph-6); 70.3 (CH2Ph-4); 33.4 (C−1).
38.5%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 21 - 24 h;
Stage #2: With hydrogenchloride; water In N,N-dimethyl-formamide
Examples; Example 1 - Preparation of 2-Hydroxy-4,6-bis(benzyloxy)- acetophenone.; [0042] This example describes the preparation and purification of the title compound from commercially available 2,4,6-trihydroxy acetophenone. A stirred suspension of 2,4,6-trihydroxyacetophenone (10 g, 0.054 mol, 1 eq) and potassium carbonate (16.3 g, 0.118 mol, 2.2 eq) in N1N- dimethylformamide (100 mL, 10 vol, 1 g/10 ml_) was heated at 8O0C. To this suspension was added benzyl chloride (13.6 mL, 0.118 mol, 2.2 eq) in one portion. The suspension was kept at 809C for about 1 h. The reaction mixture was cooled to RT and carefully acidified with 1 M hydrochloric acid (200 mL). The aqueous layer was extracted twice with ethyl acetate (100 mL) The combined organic layers were washed twice with water (100 mL) and twice with brine (100 mL), dried over sodium sulfate, and filtered. The solvent was removed under vacuum to afford a red viscous oil. The oil was dissolved in dichloromethane and passed through a 200 g plug of silica gel. The silica gel was eluted with 1 L of dichloromethane. The combined solvent was evaporated under reduced pressure to produce an oil which solidified upon standing at RT. The yield was 18.7 g. HPLC purity was 69percent purity. The product contained 19.7percent of a tribenzyl impurity. EPO <DP n="23"/>[0043] The crude solid was dissolved in hot dichloromethane (15 mL) and methanol (20 ml_) was added slowly. The solids started to appear immediately. The suspension was allowed to cool to RT with agitation. The solids were suction filtered, washed with methanol (75 mL), and dried under high vacuum to produce 9.1 g of an off-white solid. The yield was 49percent. HPLC purity was 96.9percent. The product contained about 2.54percent of the tribenzyl impurity.; A number of reaction conditions and various benzylating reagents (benzyl bromide (BnBr) and benzyl chloride (BnCI) were screened to optimize the selective benzylation. The results are set out in Table 1.

Reference: [1] Patent: CN103833720, 2016, B, . Location in patent: Paragraph 0029; 0030
[2] Chemical and Pharmaceutical Bulletin, 2013, vol. 61, # 4, p. 486 - 488
[3] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 1, p. 17 - 21
[4] Letters in Organic Chemistry, 2014, vol. 11, # 9, p. 677 - 681
[5] Patent: US2016/39781, 2016, A1, . Location in patent: Paragraph 01219; 0220
[6] Journal of Medicinal Chemistry, 2014, vol. 57, # 22, p. 9463 - 9472
[7] Patent: US2015/31639, 2015, A1, . Location in patent: Page/Page column 0079; 0080; 0081
[8] Patent: WO2007/2877, 2007, A1, . Location in patent: Page/Page column 21-23
[9] RSC Advances, 2017, vol. 7, # 29, p. 17968 - 17979
[10] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 10, p. 2263 - 2266
[11] Organic Letters, 2001, vol. 3, # 6, p. 843 - 845
[12] Patent: EP1609798, 2005, A1, . Location in patent: Page/Page column 41-42
[13] Patent: US2015/322033, 2015, A1, . Location in patent: Paragraph 0132; 0133
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YieldReaction ConditionsOperation in experiment
66.5% With potassium carbonate In N,N,N,N,N,N-hexamethylphosphoric triamide; water (a)
Preparation of 4',6'-bisbenzyloxy-2'-hydroxyacetophenone (2) from 2',4',6'-trihydroxyacetophenone (1):
A mixture of 2',4',6'-trihydroxyacetophenone (20 g, 0.12 mol, dried in the oven at 140° C.) and anhydrous potassium carbonate (50 g, 0.36 mol) in hexamethylphosphoramide (160 mL) was treated with benzyl chloride (30 mL, 0.26 mol), and the suspension heated at 90-93° C., under an argon atmosphere, for 1.5 h.
The mixture was then cooled and filtered.
The filtrate was added to 300 mL ice-cold water and acidified to pH 4 with 6N HCl.
The resulting suspension was heated to 70 ° C. for 1 h, and then cooled at 4° C. for 16 h.
The deposited sticky solid was filtered off and washed with water.
This solid was air dried, and recrystallized from boiling methanol/acetone (2:1).
Cooling the solution afforded the product 8 as off-white crystals (27.55 g, 66.5percent yield).
1H NMR (300 MHz, CDCl3): δ 2.56 (s, 3H, CH3), 5.06 (s, 4H, CH2), 6.10 and 6.16 (2s, 2H, 3',5'-Ar-H), 7.40 (m, 10H, Ar-H), 14.01 (s, 1H, OH)
Reference: [1] Patent: US2004/192723, 2004, A1,
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  • [ 61497-71-0 ]
  • [ 18065-05-9 ]
YieldReaction ConditionsOperation in experiment
49%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide at 20 - 80℃; for 1 - 7 h;
Stage #2: With hydrogenchloride; water In N,N-dimethyl-formamide
Examples; Example 1 - Preparation of 2-Hydroxy-4,6-bis(benzyloxy)- acetophenone.; [0042] This example describes the preparation and purification of the title compound from commercially available 2,4,6-trihydroxy acetophenone. A stirred suspension of 2,4,6-trihydroxyacetophenone (10 g, 0.054 mol, 1 eq) and potassium carbonate (16.3 g, 0.118 mol, 2.2 eq) in N1N- dimethylformamide (100 mL, 10 vol, 1 g/10 ml_) was heated at 8O0C. To this suspension was added benzyl chloride (13.6 mL, 0.118 mol, 2.2 eq) in one portion. The suspension was kept at 809C for about 1 h. The reaction mixture was cooled to RT and carefully acidified with 1 M hydrochloric acid (200 mL). The aqueous layer was extracted twice with ethyl acetate (100 mL) The combined organic layers were washed twice with water (100 mL) and twice with brine (100 mL), dried over sodium sulfate, and filtered. The solvent was removed under vacuum to afford a red viscous oil. The oil was dissolved in dichloromethane and passed through a 200 g plug of silica gel. The silica gel was eluted with 1 L of dichloromethane. The combined solvent was evaporated under reduced pressure to produce an oil which solidified upon standing at RT. The yield was 18.7 g. HPLC purity was 69percent purity. The product contained 19.7percent of a tribenzyl impurity. EPO <DP n="23"/>[0043] The crude solid was dissolved in hot dichloromethane (15 mL) and methanol (20 ml_) was added slowly. The solids started to appear immediately. The suspension was allowed to cool to RT with agitation. The solids were suction filtered, washed with methanol (75 mL), and dried under high vacuum to produce 9.1 g of an off-white solid. The yield was 49percent. HPLC purity was 96.9percent. The product contained about 2.54percent of the tribenzyl impurity.; A number of reaction conditions and various benzylating reagents (benzyl bromide (BnBr) and benzyl chloride (BnCI) were screened to optimize the selective benzylation. The results are set out in Table 1.
Reference: [1] Patent: WO2007/2877, 2007, A1, . Location in patent: Page/Page column 7; 21-23
[2] Patent: CN105481814, 2016, A, . Location in patent: Paragraph 0020; 0021; 0022; 0026; 0027; 0031; 0032-0042
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  • [ 584-08-7 ]
  • [ 100-44-7 ]
  • [ 18065-05-9 ]
Reference: [1] Patent: US4267165, 1981, A,
[2] Patent: US4290957, 1981, A,
[3] Patent: US4348333, 1982, A,
[4] Patent: US4226804, 1980, A,
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  • [ 18065-06-0 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1985, vol. 58, p. 136 - 141
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Reference: [1] Synthetic Communications, 1981, vol. 11, # 10, p. 853 - 858
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