18944-77-9|(E)-3-(2-Fluorophenyl)acrylic acid| Ambeed

CAS No. :	18944-77-9
Formula :	C₉H₇FO₂
M.W :	166.15
SMILES Code :	O=C(O)/C=C/C1=CC=CC=C1F
MDL No. :	MFCD00004370
InChI Key :	IOUDZAFBPDDAMK-AATRIKPKSA-N
Pubchem ID :	735833

Safety of [ 18944-77-9 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of [ 18944-77-9 ]

* 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.

Downstream synthetic route of [ 18944-77-9 ]

[ 18944-77-9 ] Synthesis Path-Downstream 1~54

1
[ 18944-77-9 ]
[ 394-46-7 ]

References: [1]Journal of the American Chemical Society,1948,vol. 70,p. 1895,1897.
[2]Bulletin de la Societe Chimique de France,1973,p. 2667 - 2668.

2
[ 18944-77-9 ]
[ 75998-36-6 ]

Yield	Reaction Conditions	Operation in experiment
36%	With pyridine; thionyl chloride; at 20 - 140℃; for 2h;	3-Chloro-4-fluorobenzo[]thiophene-2-carbonyl chloride (6)A stirred suspension of <strong>[18944-77-9]2-fluorocinnamic acid</strong> (5.0 g, 30 mmol) in thionyl chloride (7.70 mL, 0.105 mol) is treated carefully with pyridine (0.82 niL, 7.5 mmol) at RT then heated 2 h at 140C (external temperature). The refluxing reaction mixture is then treated with heptane (5 mL), heated a further 5 minutes and the resultant supernatant decanted off and cooled to 0C. The forthcoming precipitate is isolated by filtration, washed with heptane (2 x 2.5 mL) and dried to afford the title compound. Yield: 2.69 g (36%).
36%	With pyridine; thionyl chloride; at 20 - 140℃; for 2h;	3-Chloro-4-fluorobenzo[6]thiophene-2-carbonyl chloride (6); A stirred suspension of <strong>[18944-77-9]2-fluorocinnamic acid</strong> (5.0 g, 30 mmol) in thionyl chloride (7.70 mL, 0.105 mol) is treated carefully with pyridine (0.82 mL, 7.5 mmol) at RT then heated 2 h at 140C (external temperature). The refluxing reaction mixture is then treated with heptane (5 mL), heated a further 5 minutes and the resultant supernatant decanted off and cooled to 0C. The forthcoming precipitate is isolated by filtration, washed with heptane (2 x 2.5 mL) and dried to afford the title compound. Yield: 2.69 g (36%).

References: [1]Patent: WO2008/57497,2008,A2 .Location in patent: Page/Page column 203.
[2]Patent: WO2008/57468,2008,A1 .Location in patent: Page/Page column 203.
[3]Journal of Heterocyclic Chemistry,1990,vol. 27,p. 2047 - 2052.

3
[ 18944-77-9 ]
[ 120681-05-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With thionyl chloride; In N,N-dimethyl-formamide; for 4h;Reflux;	General procedure: To a solution of 1.2 equiv of substituted cinnamic acid 1a-l (5 mmol) in 5 equiv of thionyl chloride(3.6 mL), a catalytic amount of DMF was added. The reaction mixture was refluxed for 4 h, andthen, solvent was evaporated under vacuum to get the product 2a-l in the form of a solid residue inquantitative yield. The solid residue was directly added partially to an ice-cold stirred solution of1.0 equiv of tert-butyl (2-aminoethyl)carbamate or tert-butyl (3-aminopropyl)carbamate and 2.0 equivtriethylamine in DCM (20 mL). After the addition, the mixture was warmed to room temperature andstirred for 2 h. Then, DCM (20 mL) was added and washed with 0.2 M HCl (40 mL), H2O (40 mL),5% saturated. NaHCO3 (40 mL) and brine (40 mL), then dried over anhydrous magnesium sulfate.The solvent was removed in vacuo to give the corresponding cinnamamide derivatives 3a-l (65%-75%,from 1a-l) and 4a-g (59%-70%, from 1a-g) as a white solid. 3a-l, 4a-g (4 mmol) in DCM/TFA(9:1, 40 mL) were stirred at room temperature for 1 h. Solvents were removed in vacuo to yield 5a-l(100%) and 6a-g (100%) as a colorless oil.
	With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃;	2£)-3-(2-fiuorophenyl)acrylic acid (22.8 g, 134 mmol) was slurried in DCM (150 mL) and oxalyl chloride (15.5 ml, 175 mmol), and 3 drops of DMF were added. The reaction was aged at rt overnight, concentrated, and diluted with toluene (100 mL). This last step was repeated twice more to give the intermediate acid chloride. The acid chloride was dissolved in THF (150 mL) and cooled to -78 C. In a separate flask was placed (4i?)-4-benzyl-l ,3-oxazolidin-2-one (23.8 g,134 mmol) in THF (200 mL), which was cooled to -78 C. Then «-BuLi (53.8 ml, 134 mmol) was added over 15 min, and the reaction was aged 30 min. The chiral auxiliary lithiate was added over 15 min to the cooled acid chloride in THF. The reaction was aged 30 min, and then poured into an ice-cold saturated aqueous NH4C1 solution (1 L). EtOAc (200 mL) was added and the mixture was stirred for 30 min. The organic phase was separated, washed with brine (500 mL), dried (Mg2S04), filtered and concentrated. To the resulting solid was added heptane (500 mL) and EtOAc (10 mL), and the mixture stirred overnight. The solution was then filtered and the resulting solid was washed with 5% EtOAc in hexane (100 mL x 3) to give the title compound. HPLC/MS: 326.1 (M+l); Rt = 3.34 min.
	With oxalyl dichloride; N,N-dimethyl-formamide; In tetrahydrofuran; at 0℃; for 0.5h;	General procedure: General methods for 11,12-cyclic carbonate azithromycin 4"-O-(trans-β-arylacrylamido)carbamoyl analogs (5-16) To a solution of L1 (0.41 g, 2.74 mmol) in THF was added oxalyl chloride (1.03 g, 8.22 mmol) drop by drop and DMF (three drops) at 0 C. The resulting solution was stirred for 0.5 h at the same temperature. Subsequently, the reaction was quenched in vacuum to remove THF and oxalyl chloride and afforded light-yellow residue. A solution of the key intermediate 4 (3 g, 3.43 mmol) and NaHCO3 (0.23 g, 2.74 mmol) in anhydrous THF was stirred at 0 C. After addition of the above residue in THF drop by drop, the resulting solution was stirred for another 2 h at the same temperature. Then the reaction was concentrated in vacuum to remove THF and quenched with saturated NaHCO3. Subsequently, the aqueous layer was extracted with ethyl acetate (2 * 25 mL) and the combined organic layer was washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuum to afford a crude product. A solution of the above crude product in methanol was heated to 55 C and stirred for 12 h at the same temperature. Subsequent concentration of the reaction solution in vacuum provided the crude product of 5. The above crude product was purified by flash column chromatography eluting with 30:1 dichloromethane/methanol to afford the desired product 5. According to the above procedure, corresponding compounds 6-16 were prepared in yields ranging from 66% to 73%.

	With thionyl chloride; triethylamine; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 12h;	General procedure: Different substituted carboxylic acid (5mmol) and SOCl2 (7.5mmol) were dissolved into CH2Cl2 (10 mL)solvent, two drops of N, N-dimethylformamide (DMF) ascatalyst and triethylamine (TEA) (5mmol) as acid-bindingagent were added into the above solution. The reaction wasexecuted for 12 h at room temperature under continuousstirring, which was detected by TLC. Then, the redundantCH2Cl2 solvent has been removed by reduced pressuredistillation at 40∘C. Finally, the crude product of differentsubstituted acryloyl chlorides was obtained.
	With thionyl chloride; In N,N-dimethyl-formamide; toluene; at 20℃; for 3h;	General procedure: A solution of CA or CAD (1 equiv.), thionyl chloride (5 equiv.) and two drops of DMF in drytoluene was stirred at room temperature for 3 h. Solvent was evaporated. The residue
	With oxalyl dichloride; N,N-dimethyl-formamide; In tetrahydrofuran; at 0℃; for 0.5h;Inert atmosphere;	General procedure: Compound 1-4 (10 mmol, 2.5 g), ammonium chloride(10 mmol, 532 mg) and Fe (30 mmol, 1.67 g) were placed in adouble-neck flask, and 40 mL of THF and 8mL of H2Owere added tothe flask. The mixture was refluxed under nitrogen for 4 h. Whenthe reaction solution temperature cooled to room temperature,20 mL of H2O was added. The excess of Fe was filtered, and themixture was extracted with EtOAc (3 20 mL). The organic layerwas dried over anhydrous Na2SO4, filtered and concentrated toobtain the intermediate aminofuranone, which was used in thenext reaction without purification. The carboxylic acid (0.75 mmol)was added into a dry double-neck flask, and 5 mL of dry THF wasadded to the flask. N,N-Dimethylformamide (1.50 mmol, 0.15 mL)was added into the solution under nitrogen at 0 C. When thesewere completely dissolved, oxalyl chloride (3.75 mmol) was addedslowly. After 30 min, the solvent and excess oxalyl chloride werethen removed under reduced pressure to obtain an acyl chloride.The acyl chloride was kept dry. 100 mg of the intermediate aminofuranone was added into a dry double-neck flask, and 5 mL of dryTHFwas added to the flask. When these were completely dissolved,dry pyridine (1.06 mmol, 0.01 mL) was added under nitrogen at0 C. The THF solution of an acyl chloride (0.793 mmol) was addedinto the mixture slowly. After 30 min, 20 mL of saturated ammoniumchloride solution was slowly added into the mixture, and themixture was extracted three times with EtOAc (3 x 20 mL). Theorganic layer was dried over anhydrous Na2SO4, filtered andconcentrated to dryness, which was purified through silica gelcolumn (EA: PE 2: 1) to give A-1~A-7.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 5h;Inert atmosphere;	General procedure: To a solution of cinnamic acid (1a01e24, 1a26e27, 1a29)(1.0 mmol) in dry CH2Cl2 was added oxalyl chloride (5.0 equiv) anda catalytic amount of DMF (0.01 equiv). The reaction mixture wasstirred at room temperature for 5 h before the solvent wasremoved. The residuewas dried under high vacuum and used in thenext step without further purification.

References: [1]Molecules,2016,vol. 21.
[2]Synthetic Communications,1997,vol. 27,p. 883 - 895.
[3]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 4426 - 4434.
[4]Patent: WO2011/146300,2011,A1 .Location in patent: Page/Page column 56.
[5]Chemical Communications,2014,vol. 50,p. 4459 - 4461.
[6]Journal of Organic Chemistry,2014,vol. 79,p. 3537 - 3546.
[7]European Journal of Medicinal Chemistry,2015,vol. 103,p. 506 - 515.
[8]Journal of Chemistry,2016,vol. 2016.
[9]Molecules,2016,vol. 21.
[10]European Journal of Medicinal Chemistry,2017,vol. 127,p. 187 - 199.
[11]Journal of Organic Chemistry,2017,vol. 82,p. 9627 - 9636.
[12]Organic and Biomolecular Chemistry,2017,vol. 15,p. 9804 - 9808.
[13]Chemical Communications,2018,vol. 54,p. 13941 - 13944.
[14]Drug Development Research,2019,vol. 80,p. 438 - 445.
[15]European Journal of Medicinal Chemistry,2019,vol. 167,p. 414 - 425.
[16]RSC Advances,2020,vol. 10,p. 42128 - 42136.
[17]Journal of Natural Products,2021,vol. 84,p. 1954 - 1966.
[18]Crystal Growth and Design,2021,vol. 21,p. 4162 - 4177.
[19]Journal of Agricultural and Food Chemistry,2021,vol. 69,p. 12156 - 12170.
[20]Journal of Agricultural and Food Chemistry,2021,vol. 69,p. 12621 - 12633.
[21]Chemistry and biodiversity,2022,vol. 19.

4
coenzyme A trilithium salt [ No CAS ]
[ 18944-77-9 ]
C₃₀H₄₁FN₇O₁₇P₃S [ No CAS ]

References: [1]Organic Letters,2007,vol. 9,p. 1855 - 1858.

5
[ 18944-77-9 ]
[ 807369-87-5 ]

References: [1]Organic Letters,2007,vol. 9,p. 3949 - 3952.
[2]Advanced Synthesis and Catalysis,2015,vol. 357,p. 2442 - 2446.
[3]Chemistry - An Asian Journal,2020,vol. 15,p. 555 - 559.

6
[ 18944-77-9 ]
2,2,2-trifluoro-N-(1-(2-fluorophenyl)allyl)acetamide [ No CAS ]

References: [1]Organic Letters,2007,vol. 9,p. 3949 - 3952.

7
[ 18944-77-9 ]
2,2,2-trifluoro-N-(1-(2-fluorophenyl)allyl)acetamide [ No CAS ]

References: [1]Organic Letters,2007,vol. 9,p. 3949 - 3952.

8
[ 18944-77-9 ]
[ 143654-59-5 ]

Yield	Reaction Conditions	Operation in experiment
100%		In a Parr hydrogenation vessel is placed <strong>[18944-77-9]2-fluorocinnamic acid</strong> (1h) (1.0 equiv) and palladium on carbon in a 1/1 methanol/ethyl acetate solution. The heterogeneous solution is placed on a Parr shaker and treated with hydrogen (50 psi) until uptake has ceased. The mixture is filtered through Celite and concentrated under reduced pressure. The residue is taken up in diethyl ether and is treated with diazomethane until the yellow color persists. The solution is concentrated under reduced pressure giving the crude methyl ester. Purification is effected by column chromatography on silica gel (hexane/ethyl acetate 5/1) to yield Methyl 3-(2-fluorophenyl)propionate (1i) in quantitative yield.

References: [1]Patent: US6410780,2002,B1 .Location in patent: Page column 15.
[2]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 1519 - 1522.

9
[ 18944-77-9 ]
[ 221631-40-9 ]