Home Cart 0 Sign in  
X

[ CAS No. 108-55-4 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 108-55-4
Chemical Structure| 108-55-4
Chemical Structure| 108-55-4
Structure of 108-55-4 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 108-55-4 ]

Related Doc. of [ 108-55-4 ]

Alternatived Products of [ 108-55-4 ]

Product Details of [ 108-55-4 ]

CAS No. :108-55-4 MDL No. :MFCD00006679
Formula : C5H6O3 Boiling Point : -
Linear Structure Formula :- InChI Key :VANNPISTIUFMLH-UHFFFAOYSA-N
M.W : 114.10 Pubchem ID :7940
Synonyms :

Calculated chemistry of [ 108-55-4 ]

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.6
Num. rotatable bonds : 0
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 25.52
TPSA : 43.37 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 : No
Log Kp (skin permeation) : -7.07 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.82
Log Po/w (XLOGP3) : -0.1
Log Po/w (WLOGP) : 0.24
Log Po/w (MLOGP) : 0.33
Log Po/w (SILICOS-IT) : 1.28
Consensus Log Po/w : 0.51

Druglikeness

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

Water Solubility

Log S (ESOL) : -0.48
Solubility : 37.4 mg/ml ; 0.328 mol/l
Class : Very soluble
Log S (Ali) : -0.36
Solubility : 50.0 mg/ml ; 0.438 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.73
Solubility : 21.3 mg/ml ; 0.187 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.27

Safety of [ 108-55-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P264-P271-P280-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 108-55-4 ]

* 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 [ 108-55-4 ]
  • Downstream synthetic route of [ 108-55-4 ]

[ 108-55-4 ] Synthesis Path-Upstream   1~27

  • 1
  • [ 108-55-4 ]
  • [ 494-52-0 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 20, p. 4381 - 4388
  • 2
  • [ 108-55-4 ]
  • [ 3543-73-5 ]
Reference: [1] Patent: US2014/31560, 2014, A1,
[2] Patent: EP2690096, 2014, A1,
  • 3
  • [ 108-55-4 ]
  • [ 3543-72-4 ]
Reference: [1] Patent: US2014/31560, 2014, A1,
[2] Patent: EP2690096, 2014, A1,
  • 4
  • [ 108-55-4 ]
  • [ 3543-74-6 ]
Reference: [1] Patent: EP2690096, 2014, A1,
[2] Patent: EP2690096, 2014, A1,
[3] Patent: US2014/31560, 2014, A1,
  • 5
  • [ 108-55-4 ]
  • [ 96-48-0 ]
  • [ 3136-17-2 ]
  • [ 1487-49-6 ]
  • [ 29006-01-7 ]
  • [ 1732-08-7 ]
  • [ 1732-09-8 ]
Reference: [1] J. Appl. Chem. USSR (Engl. Transl.), 1987, vol. 60, # 11, p. 2428 - 2429[2] Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation), 1987, vol. 60, # 11, p. 2619 - 2620
  • 6
  • [ 67-56-1 ]
  • [ 108-55-4 ]
  • [ 1501-27-5 ]
Reference: [1] Advanced Synthesis and Catalysis, 2007, vol. 349, # 3, p. 432 - 440
[2] Chemical Communications, 2016, vol. 52, # 49, p. 7715 - 7718
[3] Biochemical Journal, 1925, vol. 19, p. 393
[4] Journal of the Chemical Society, 1947, p. 1108
[5] Journal of the American Chemical Society, 1965, vol. 87, p. 1984 - 1990
[6] Tetrahedron, 1995, vol. 51, # 3, p. 695 - 702
[7] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 6, p. 1543 - 1546
[8] Journal of Organic Chemistry, 2006, vol. 71, # 12, p. 4565 - 4577
[9] European Journal of Medicinal Chemistry, 2009, vol. 44, # 4, p. 1638 - 1643
[10] Patent: WO2012/25474, 2012, A1, . Location in patent: Page/Page column 29
[11] Letters in Drug Design and Discovery, 2011, vol. 8, # 6, p. 500 - 505
[12] Chemistry and Physics of Lipids, 2014, vol. 184, p. 105 - 118
[13] European Journal of Medicinal Chemistry, 2016, vol. 116, p. 126 - 135
  • 7
  • [ 108-55-4 ]
  • [ 124-41-4 ]
  • [ 1501-27-5 ]
Reference: [1] Journal of Organic Chemistry, 2000, vol. 65, # 3, p. 707 - 715
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 21, p. 8948 - 8952
  • 8
  • [ 67-56-1 ]
  • [ 108-55-4 ]
  • [ 124-41-4 ]
  • [ 1501-27-5 ]
Reference: [1] Patent: WO2006/137080, 2006, A1, . Location in patent: Page/Page column 11
[2] Patent: WO2008/32338, 2008, A2, . Location in patent: Page/Page column 17
  • 9
  • [ 108-55-4 ]
  • [ 917-58-8 ]
  • [ 1501-27-5 ]
Reference: [1] Acta Chemica Scandinavica (1947-1973), 1955, vol. 9, p. 1674,1678
  • 10
  • [ 67-56-1 ]
  • [ 108-55-4 ]
  • [ 1501-26-4 ]
YieldReaction ConditionsOperation in experiment
86.4%
Stage #1: for 1 h; Reflux
Stage #2: With thionyl chloride In N,N-dimethyl-formamide for 2 h;
100 g (0.878 mol) of glutaric anhydride was dissolved in 50 mL of anhydrous methanol, heated to reflux for 1 h, and then distilled under reduced pressure to remove unreacted methanol,The reaction solution was cooled to room temperature,Add 200 mL slowlyThionyl chloride and 6 drops of DMF,After heating for 2 hours, the water pump was distilled under reduced pressure, and the remaining sodium dichlorosulfoxide was removed. Then, the fraction was dried at a pressure of 96 ° C to 98 ° C / 10 mmHg to obtain 124.2 g of a pale yellow liquid in a yield of 86.4percent.
Reference: [1] Patent: CN103864658, 2016, B, . Location in patent: Paragraph 0056; 0057
[2] Tetrahedron Letters, 1984, vol. 25, # 39, p. 4371 - 4374
[3] Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, vol. 31, # 6, p. 915 - 923
  • 11
  • [ 108-55-4 ]
  • [ 1501-26-4 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 6, p. 1543 - 1546
[2] Tetrahedron, 1995, vol. 51, # 3, p. 695 - 702
[3] Journal of the Chemical Society, 1947, p. 1108
[4] Biochemical Journal, 1925, vol. 19, p. 393
[5] Journal of the American Chemical Society, 1965, vol. 87, p. 1984 - 1990
[6] Journal of Medicinal Chemistry, 2013, vol. 56, # 21, p. 8948 - 8952
[7] European Journal of Medicinal Chemistry, 2016, vol. 116, p. 126 - 135
  • 12
  • [ 108-55-4 ]
  • [ 64-17-5 ]
  • [ 1070-62-8 ]
Reference: [1] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1877, vol. 9, p. 283[2] Chemische Berichte, 1877, vol. 10, p. 1103
[3] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1877, vol. 9, p. 283[4] Chemische Berichte, 1877, vol. 10, p. 1103
[5] Journal of Organic Chemistry, 2003, vol. 68, # 23, p. 8950 - 8963
[6] Journal of Organic Chemistry, 1961, vol. 26, p. 3183 - 3186
[7] Acta Chemica Scandinavica (1947-1973), 1963, vol. 17, p. 2423 - 2436
[8] Synthetic Communications, 1988, vol. 18, # 14, p. 1691 - 1698
[9] Bulletin des Societes Chimiques Belges, 1991, vol. 100, # 7, p. 555 - 560
  • 13
  • [ 108-55-4 ]
  • [ 141-52-6 ]
  • [ 1070-62-8 ]
Reference: [1] Recueil des Travaux Chimiques des Pays-Bas, 1907, vol. 26, p. 381
  • 14
  • [ 67-56-1 ]
  • [ 108-55-4 ]
  • [ 1119-40-0 ]
YieldReaction ConditionsOperation in experiment
96% at 20℃; for 18 h; Glutaric anhydride (29.4 mmol, 3.35 g) was dissolved in anhydrous MeOH (100 mL) and conc. H2SO4 (5.9 mmol, 0.31 mL) was added. After being stirred at room temperature for 18 h, the mixture was concentrated to a half volume and quenched with water (40 mL) afterwards. The aqueous phase was extracted with CH2Cl2 (3 x 50 mL), the combined organic phases were washed with brine (30 mL), dried over Na2SO4 and concentrated to give dimethyl glutarate 1l (4.53 g, 96percent) as a colourless clear oil; 1H NMR (CDCl3): δ =1.96 (quint, J = 7.2 Hz, 2H), 2.39 (t, J = 7.2 Hz, 4H).
Reference: [1] Tetrahedron, 2015, vol. 71, # 47, p. 8871 - 8875
  • 15
  • [ 108-55-4 ]
  • [ 1119-40-0 ]
Reference: [1] Journal of the Indian Chemical Society, 2012, vol. 89, # 7, p. 975 - 979
  • 16
  • [ 108-55-4 ]
  • [ 1121-89-7 ]
  • [ 1119-40-0 ]
  • [ 1732-09-8 ]
  • [ 4567-98-0 ]
Reference: [1] J. Appl. Chem. USSR (Engl. Transl.), 1987, vol. 60, # 11, p. 2428 - 2429[2] Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation), 1987, vol. 60, # 11, p. 2619 - 2620
  • 17
  • [ 108-55-4 ]
  • [ 108-86-1 ]
  • [ 35333-26-7 ]
YieldReaction ConditionsOperation in experiment
85%
Stage #1: With aluminum (III) chloride In dichloromethane at 7℃; for 0.5 h;
Stage #2: at 20℃; for 19 h;
A flask was charged with AlCl3 (78.8 mmol, 10.5 g, 2.3 equiv) and dry CH2Cl2 (25 ml) under calcium chloride guard tube and the formed suspension was stirred on ice bath. Subsequently, a solution of glutaric anhydride 10 (34.3 mmol, 3.91 g) in dry CH2Cl2 (15 ml) was added dropwise (t < 7 °C). The resulting mixture was stirred on ice bath for 30 minutes and bromobenzene 11b (34.3 mmol, 5.39 g, 1.0 equiv) was carefully added afterwards. The cooling bath was removed and the mixture was stirred at room temperature for 19 hours, then it was poured into ice water (15 ml), acidified with conc. H2SO4 (10 ml), the aqueous layer was extracted with ethyl acetate (1 x 100 ml, 2 x 50 ml), the combined organics were dried over Na2SO4, filtered and concentrated. The crude product was dissolved in ethyl acetate and the resulting solution was added dropwise to a vigorously stirred cold hexanes (1 L). The precipitate was filtered off and dried to provide 5-(4-bromophenyl)-5-oxopentanoic acid (7.93 g, 85percent) as a yellow powder;2 mp 125-127 °C; 1H NMR (300 MHz, CDCl3): δ = 2.07 (m, 2H), 2.50 (t, J = 7.2 Hz, 2H), 3.04 (t, J = 7.2 Hz, 2H), 7.60 (m, 2H), 7.82 (m, 2H). 5-(4-Bromophenyl)-5-oxopentanoic acid (25.0 mmol, 6.78 g), paraformaldehyde (86.3 mmol, 2.59 g, 3.4 equiv) and piperidine (0.57 ml, 0.24 equiv) were dissolved/suspended in pyridine (42 ml) and stirred at 70 °C for 21 hours. Afterwards, the mixture was poured into 1M H2SO4 (200 ml)/conc. H2SO4 (15 ml), the aqueous layer was extracted with ethyl acetate (1 x 150 ml, 2 x 100 ml), the combined organics were washed with half-saturated brine (300 ml), dried over Na2SO4, filtered and concentrated. The crude product was crystallized from ethyl acetate to yield 4-(4-bromobenzoyl)pent-4-enoic acid 9b (3.93 g, 56percent) as an orange-yellow solid; mp 127-128 °C; 1H NMR (300 MHz, CDCl3): δ = 2.63 (t, J = 6.9 Hz, 2H), 2.80 (t, J = 6.9 Hz, 2H), 5.67 (s, 1H), 5.95 (s, 1H), 7.60 (m, 4H); 13C NMR (75 MHz, CDCl3): δ = 27.2, 32.6, 127.3, 127.4, 131.0, 131.6, 136.3, 145.8, 178.9, 196.6.
Reference: [1] Russian Journal of General Chemistry, 2014, vol. 84, # 9, p. 1825 - 1829[2] Zhurnal Obshchei Khimii, 2014, vol. 84, # 9, p. 1825 - 1829,5
[3] Tetrahedron Letters, 2016, vol. 57, # 10, p. 1079 - 1082
[4] Heterocycles, 2005, vol. 65, # 3, p. 649 - 656
  • 18
  • [ 108-55-4 ]
  • [ 100-51-6 ]
  • [ 54322-10-0 ]
YieldReaction ConditionsOperation in experiment
67% With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; General procedure: To a solution of succinic anhydride (1.0g, 10mmol) in DMF (4mL) was added benzyl alcohol (0.94mL, 9.09mmol) and DIEA (1.93mL, 11mmol) at 0°C. The reaction mixture was stirred at room temperature overnight and was evaporated in Speed-vac. The residue was dissolved in ethyl acetate (50mL) and washed with saturated NaCl (10mL×2). The organic solution was extracted with aqueous NaHCO3 (5M, 5mL×3) and the aqueous extractions were combined, acidified to pH 4 by adding citric acid (5M), extracted with ethyl acetate (30mL×3). The EtOAc extractions were combined, washed with saturated NaCl, and dried over Na2SO4. Solvent was removed by evaporation in vacuo to give a white solid (1.66g, 89percent);
64% With dmap In dichloromethane at 25℃; for 24 h; Inert atmosphere; Large scale [0284] To a solution of oxane-2, 6-dione (1000 g, 8.76 mol, 1.00 equiv.), 4- dimethylaminopyridine (53.5 g, 437.9 mmol, 0.05 equiv.) in dichloromethane (10000 mL) with an inert atmosphere of nitrogen was added phenylmethanol (900 g, 8.32 mol, 0.95 equiv.) dropwise with stirring at room temperature. The resulting solution was stirred overnight at room temperature. The resulting mixture was washed with saturated sodium bicarbonate solution. The pH value of the aqueous layers was adjusted to 1 with 10percent hydrochloric acid. The resulting solution was extracted with 3x2000 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2x3000 mL of saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. This resulted in 1240 g (64percent) of G-1 as colorless oil. MS m/z [M+H]+ (ESI): 223.
Reference: [1] Chemical Biology and Drug Design, 2018, vol. 92, # 2, p. 1403 - 1408
[2] Synthetic Communications, 2001, vol. 31, # 9, p. 1399 - 1419
[3] Journal of the American Chemical Society, 1996, vol. 118, # 29, p. 6826 - 6840
[4] Chemical Communications, 2011, vol. 47, # 17, p. 4896 - 4898
[5] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 23, p. 7507 - 7514
[6] Patent: WO2018/53185, 2018, A1, . Location in patent: Paragraph 0284
[7] Tetrahedron Letters, 1996, vol. 37, # 31, p. 5427 - 5430
[8] Journal of Medicinal Chemistry, 1990, vol. 33, # 1, p. 344 - 347
[9] Journal of the American Chemical Society, 1995, vol. 117, # 8, p. 2123 - 2127
[10] Journal of Pharmacy and Pharmacology, 2002, vol. 54, # 3, p. 349 - 364
[11] Journal of the American Chemical Society, 1956, vol. 78, p. 2341,5920
[12] Tetrahedron Letters, 1996, vol. 37, # 50, p. 9033 - 9036
[13] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 16, p. 2109 - 2114
[14] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 21, p. 5295 - 5300
[15] Tetrahedron Asymmetry, 2005, vol. 16, # 14, p. 2509 - 2513
[16] Patent: WO2009/157019, 2009, A2, . Location in patent: Page/Page column 18-19
[17] Patent: US2010/286225, 2010, A1, . Location in patent: Page/Page column 4
  • 19
  • [ 108-55-4 ]
  • [ 2785-29-7 ]
  • [ 54322-10-0 ]
Reference: [1] Acta Chemica Scandinavica (1947-1973), 1955, vol. 9, p. 1674,1678
  • 20
  • [ 108-55-4 ]
  • [ 4654-08-4 ]
Reference: [1] Organic and Biomolecular Chemistry, 2015, vol. 13, # 39, p. 9977 - 9983
  • 21
  • [ 108-55-4 ]
  • [ 127310-66-1 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6771 - 6777
[2] Patent: WO2017/15106, 2017, A1,
  • 22
  • [ 108-55-4 ]
  • [ 3543-75-7 ]
Reference: [1] Patent: EP2690096, 2014, A1,
[2] Patent: EP2690096, 2014, A1,
[3] Patent: US2014/31560, 2014, A1,
  • 23
  • [ 108-55-4 ]
  • [ 462-06-6 ]
  • [ 149437-76-3 ]
YieldReaction ConditionsOperation in experiment
85% at 0℃; for 0.5 h; To a stirred suspension of aluminum chloride (205.85g, 1. 54MOL) in dichloromethane(500ML) was added a solution of glutaric anhydride (80g, 0. 7MOL) indichloromethane (125ML) at 0C. The reaction mass was stirred for30minutes and fluorobenzene (67.36g, 0. 7MOL) was added to the reactionmass slowly. The reaction was monitored for completion by TLC and thenpoured into ice cold water (2000ML) under stirring and the separatedsolids were collected by filtration. The solids were dissolved in 3percentaqueous sodium hydroxide solution (1100ML) and washed withdichloromethane (300ML). The aqueous layer was acidified to give aprecipitate. The solids were filtered and washed with water andvacuum-dried to yield the title product (125g, yield: 85percent). LHNMR(CDC13) 8 : 8.027-7. 98 (M, 2H), 7.17-7. 11 (M, 2H), 3.067 (t, 2H), 2.52(t, 2H), 2.14-2. 04 (M, 2H).
82%
Stage #1: at 15 - 30℃; for 5 h;
Stage #2: at 0 - 20℃;
In a milliliter three-necked flask, 200 ml of fluorobenzene was added, Then aluminum trichloride (59.4 g, 0.45 mol) was added,And cooled to 15 ° C with an ice bath, Then, the solution of glutaric anhydride (30 g, 0.3 mol) in fluorobenzene (100 ml) was added dropwise at 15 ° C, After completion of the dropwise reaction at 30 ° C for 5 hours,Cold to about 0 deg C, Dropping 200 ml of 1 M hydrochloric acid, Note that the temperature during the dropwise process does not exceed 20 ° C. After completion of the dropwise addition, the reaction solution was added to a large amount of ice water, Precipitation of solids, filter, Wash the filter cake with steamed water, The filter cake was then added to 800 ml of saturated sodium bicarbonate solution and stirred at room temperature for 1 h, filter, The filtrate was added with activated carbon decolorization. Concentrated hydrochloric acid to adjust the PH value to 1, Solid precipitation, Filter and wash the filter cake with water, After drying, 51.7 g of white solid compound I, Yield 82percent.
79.3% at 5 - 20℃; for 2.25 h; EXAMPLES; Starting materials useful in the processes of the present invention can be made by the following procedures: Preparation of 4-(4-fluorobenzoyl)butyric acid; Charged 250 g of anhydrous AlCl3 (1.87 moles) to a 2 L 3-neck round bottom flask, added 300 mL fluorobenzene (307.5 g; 3.2 moles) and cooled the mixture in an ice bath to 5° C. Added a hazy suspension of 100 g glutaric anhydride (0.86 mole) in 400 mL fluorobenzene (4.3 moles) through an addition funnel over a period of 45 min., and maintained the temperature below 12° C. The reaction mixture was warmed to ambient temperature gradually and agitated at r.t. for about 90 min.; checked for completion by NMR. Cooled the reaction mixture to 0 to 5° C., then added a cold aqueous solution (700 mL) of 1N HCl carefully to the mixture to destroy any unreacted AlCl3, keeping the temperature of the mixture below 20° C. during the early part of the acid addition, and below 40° C. for the rest of the time. Poured the entire mixture into a 2 L 1:1 mixture of water and ice (v/w) to precipitate out crude products, filtered the white suspension and washed well with water. Added the white residue to 3 L of aqueous saturated solution (5percent) of NaHCO3, heated the basic mixture on a steam bath for one hour and filtered the batch while hot through a thin pad of celite. Cooled the filtrate to r.t., added about 320 mL of concentrated HCl dropwise into the filtrate to pH 1 to crystallize out products, and agitated the white suspension in an ice bath for 30 min. Filtered the batch, washed the wet cake with ice cold water and dried in a vacuum oven at 50° C. for 16 h to obtain 143.2 g of 4-(4-fluorobenzoyl)-butyric acid; m.p. 141 to 142° C., isolated yield: 79.3percent.
79.3% at 5 - 20℃; for 2.25 h; Charge 250 g of anhydrous AlCl3 (1.87 moles) to a 2 L 3-neck round bottom flask, add 300 mL fluorobenzene (307.5 g; 3.2 moles) and cool the mixture in an ice bath to 5°C. Add a hazy suspension of 100 g glutaric anhydride (0.86 mole) in 400 mL fluorobenzene (4.3 moles) through an addition funnel over a period of 45 min., and maintain the temperature below 12°C.
Warm the reaction mixture to ambient temperature gradually and agitate at r.t. for about 90 min.; check for completion by NMR.
Cool the reaction mixture to 0 to 5°C, then add a cold aqueous solution (700 mL) of 1 N HCl carefully to the mixture to destroy any unreacted AlCl3, keeping the temperature of the mixture below 20°C during the early part of the acid addition, and below 40°C for the rest of the time.
Pour the entire mixture into a 2 L 1:1 mixture of water and ice (v/w) to precipitate out crude products, filter the white suspension and wash well with water.
Add the white residue to 3 L of aqueous saturated solution (~5percent) of NaHCO3, heat the basic mixture on a steam bath for one hour and filter the batch while hot through a thin pad of celite.
Cool the filtrate to r.t., add about 320 mL of concentrated HCl dropwise into the filtrate to pH 1 to crystallize out products, and agitate the white suspension in an ice bath for 30 min.
Filter the batch, wash the wet cake with ice cold water and dry in a vacuum oven at 50°C for 16 h to obtain 143.2 g of 4-(4-fluorobenzoyl)-butyric acid; m.p. 141 to 142°C, isolated yield: 79.3percent.
51%
Stage #1: With aluminum (III) chloride In dichloromethane at 8℃; for 0.5 h;
Stage #2: at 20℃; for 19 h;
A flask was charged with AlCl3 (77.17 mmol, 10.29 g, 2.15 equiv) and dry CH2Cl2 (25 ml) under calcium chloride guard tube and the formed suspension was stirred on ice bath. Subsequently, a solution of glutaric anhydride 10 (35.8 mmol, 4.08 g) in dry CH2Cl2 (12 ml) was added dropwise (t < 8 °C). The resulting mixture was stirred on ice bath for 30 minutes and fluorobenzene 11c (35.1 mmol, 3.37 g, 1.0 equiv) was carefully added afterwards. The cooling bath was removed and the mixture was stirred at room temperature for 19 hours, then it was carefully quenched with ice water (20 ml), conc. H2SO4 (10 ml) and again with ice water (60 ml), the aqueous layer was extracted with ethyl acetate (1 x 200 ml, 1 x 100 ml, 1 x 70 ml), the combined organics were washed with half-saturated brine (200 ml), dried over Na2SO4, filtered and concentrated. The crude product was crystallized from ethyl acetate to provide 5-(4-fluorophenyl)-5-oxopentanoic acid (3.80 g, 51percent) as a yellow-brown powder;3 mp 141-142 °C; 1H NMR (300 MHz, CDCl3): δ = 2.08 (m, 2H), 2.51 (t, J = 7.2 Hz, 2H), 3.05 (t, J = 7.2 Hz, 2H), 7.13 (m, 2H), 7.99 (m, 2H). 5-(4-Fluorophenyl)-5-oxopentanoic acid (16.7 mmol, 3.50 g), paraformaldehyde (50.0 mmol, 1.50 g, 3.0 equiv) and piperidine (0.32 ml, 0.2 equiv) were dissolved/suspended in pyridine (15 ml) and stirred at 70 °C for 21 hours. Afterwards, the mixture was poured into 1M H2SO4 (340 ml), the aqueous layer was extracted with ethyl acetate (4 x 100 ml), the combined organics were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (EA/hexanes = 1/1 + 0.5percent AcOH). The obtained product was repeatedly coevaporated with toluene (4 x 25 ml) under reduced pressure to remove the residual AcOH, yielding 4-(4-fluorobenzoyl)pent-4-enoic acid 9c (3.33 g, 90percent) as an orange solid; mp 81-82 °C; 1H NMR (300 MHz, CDCl3): δ = 2.62 (t, J = 7.2 Hz, 2H), 2.80 (t, J = 7.2 Hz, 2H), 5.65 (s, 1H), 5.92 (s, 1H), 7.12 (dd, J = 8.7, 8.7 Hz, 2H), 7.78 (dd, J = 5.7, 8.7 Hz, 2H), 10.74 (bs, 1H); 13C NMR (75 MHz, CDCl3): δ = 27.3, 32.5, 115.3 (d, JCF = 21.8 Hz), 126.7, 132.0 (d, JCF = 9.0 Hz), 133.7, 145.9, 165.3 (d, JCF = 252.5 Hz), 178.9, 196.2
125 g
Stage #1: With aluminum (III) chloride In dichloromethane at 0℃; for 0.5 h;
To a suspension of aluminum chloride (205.85 g, 1.54 mol) in dichloromethane (500 mL) was added a solution of glutaric anhydride (80 g, 0.7 mol) in dichloromethane (125 mL) at 0° C.
The reaction mixture was stirred for 30 minutes.
Fluorobenzene (67.36 g, 0.7 mol) was then added slowly.
The progress of the reaction was monitored by TLC. Upon completion, the reaction mixture was poured into ice water (2000 mL) to precipitate a crude solid product, which was collected by filtration.
The crude was re-dissolved in a 3percent aqueous sodium hydroxide solution (1100 mL).
After being washed with dichloromethane (300 mL), the aqueous solution was acidified to obtain a solid product.
The product was filtered, washed with water, and vacuum dried to yield compound 3 (125 g). H NMR of compound 3 (CDCl3, 300M Hz): δ=2.10 (q, J=7.2 Hz, 2H), 2.51 (t, J=7.2 Hz, 2H), 3.65 (t, J=7.2 Hz, 2H), 7.13 (t, J=7.4 Hz, 2H), 7.98 (q, J=5.4 Hz, 2H)
10 g With aluminum (III) chloride In dichloromethane at 20℃; 25 gms of Aluminium chloride was added to 50 ml of dichloromethane and 4.5 ml of fluorobenzene. To this a solution of 50 ml of dichloromethane containing 10 gms of glutaric anhydride and 4.5 ml of fluorobenzene was added. Reaction mass was stirred at room temperature. After completion of reaction, reaction mass was quenched with ice& HCl solution at 0-10° C. Filtered the reaction mass. The obtained wet solid was dissolved in eq NaHCO3 solution at 60-70° C. and insoluable material was filtered. Cooled the filtrate and adjust pH to 2.0 by adding hydrochioric acid. Obtained solid was filtered and dried at 60-70° C. under vacuum to get 10 gm of 5-(4-Fluoro-phenyl)-5-oxo-pentanoic acid.

Reference: [1] Patent: WO2004/99132, 2004, A2, . Location in patent: Page 7-8
[2] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 15, p. 4424 - 4426
[3] Patent: CN106397292, 2017, A, . Location in patent: Paragraph 0053; 0083; 0084
[4] Patent: US2006/135755, 2006, A1, . Location in patent: Page/Page column 15
[5] Patent: EP1137634, 2005, B1, . Location in patent: Page/Page column 9
[6] Tetrahedron, 1993, vol. 49, # 15, p. 3193 - 3202
[7] Tetrahedron Letters, 2016, vol. 57, # 10, p. 1079 - 1082
[8] Patent: WO2003/104180, 2003, A1, . Location in patent: Page 6-8
[9] Patent: WO2003/104180, 2003, A1, . Location in patent: Page 9
[10] Patent: WO2007/17705, 2007, A1, . Location in patent: Page/Page column 12
[11] Patent: US2015/18565, 2015, A1, . Location in patent: Paragraph 0035; 0036; 0037
[12] Patent: US2016/280642, 2016, A1, . Location in patent: Paragraph 0056
[13] Patent: CN103694111, 2016, B, . Location in patent: Paragraph 0032-0035; 0042
[14] Chirality, 2018, vol. 30, # 5, p. 642 - 651
  • 24
  • [ 108-55-4 ]
  • [ 352-13-6 ]
  • [ 149437-76-3 ]
Reference: [1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 9, p. 2723 - 2730
  • 25
  • [ 108-55-4 ]
  • [ 250249-85-5 ]
Reference: [1] Organic letters, 2001, vol. 3, # 2, p. 193 - 196
  • 26
  • [ 108-55-4 ]
  • [ 68419-38-5 ]
Reference: [1] Organic letters, 2001, vol. 3, # 2, p. 193 - 196
  • 27
  • [ 108-55-4 ]
  • [ 189028-93-1 ]
Reference: [1] Patent: CN106397292, 2017, A,
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 108-55-4 ]

Acid anhydrides

Chemical Structure| 185815-59-2

[ 185815-59-2 ]

4-Isobutyldihydro-2H-pyran-2,6(3H)-dione

Similarity: 0.93

Chemical Structure| 108-30-5

[ 108-30-5 ]

Dihydrofuran-2,5-dione

Similarity: 0.88

Chemical Structure| 5617-74-3

[ 5617-74-3 ]

3-Oxabicyclo[3.1.0]hexane-2,4-dione

Similarity: 0.81

Chemical Structure| 13080-96-1

[ 13080-96-1 ]

Acetic propionic anhydride

Similarity: 0.80

Chemical Structure| 67911-21-1

[ 67911-21-1 ]

6,6-Dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione

Similarity: 0.78

Esters

Chemical Structure| 185815-59-2

[ 185815-59-2 ]

4-Isobutyldihydro-2H-pyran-2,6(3H)-dione

Similarity: 0.93

Chemical Structure| 123-29-5

[ 123-29-5 ]

Ethyl nonanoate

Similarity: 0.92

Chemical Structure| 818-38-2

[ 818-38-2 ]

Diethyl glutarate

Similarity: 0.92

Chemical Structure| 3681-78-5

[ 3681-78-5 ]

Propyl dodecanoate

Similarity: 0.92

Chemical Structure| 124-06-1

[ 124-06-1 ]

Ethyl tetradecanoate

Similarity: 0.92

Related Parent Nucleus of
[ 108-55-4 ]

Tetrahydropyrans

Chemical Structure| 185815-59-2

[ 185815-59-2 ]

4-Isobutyldihydro-2H-pyran-2,6(3H)-dione

Similarity: 0.93

Chemical Structure| 103260-44-2

[ 103260-44-2 ]

Ethyl 2-(tetrahydro-2H-pyran-4-yl)acetate

Similarity: 0.89

Chemical Structure| 713-95-1

[ 713-95-1 ]

6-Heptyltetrahydro-2H-pyran-2-one

Similarity: 0.86

Chemical Structure| 710-04-3

[ 710-04-3 ]

6-Hexyltetrahydro-2H-pyran-2-one

Similarity: 0.86

Chemical Structure| 156002-64-1

[ 156002-64-1 ]

Methyl 2-(tetrahydro-2H-pyran-4-yl)acetate

Similarity: 0.85