[ CAS No. 331-39-5 ] {[proInfo.proName]}

Name: 331-39-5|3-(3,4-Dihydroxyphenyl)acrylic acid|98%
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Quality Control of [ 331-39-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 331-39-5 ]

Product Details of [ 331-39-5 ]

CAS No. :	331-39-5	MDL No. :	MFCD00004392
Formula :	C₉H₈O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QAIPRVGONGVQAS-DUXPYHPUSA-N
M.W :	180.16	Pubchem ID :	689043
Synonyms :	3,4-Dihydroxycinnamic Acid

Calculated chemistry of [ 331-39-5 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	3.0
Molar Refractivity :	47.16
TPSA :	77.76 Å²

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) :	-6.58 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.97
Log Po/w (XLOGP3) :	1.15
Log Po/w (WLOGP) :	1.09
Log Po/w (MLOGP) :	0.7
Log Po/w (SILICOS-IT) :	0.75
Consensus Log Po/w :	0.93

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-1.89
Solubility :	2.32 mg/ml ; 0.0129 mol/l
Class :	Very soluble
Log S (Ali) :	-2.38
Solubility :	0.755 mg/ml ; 0.00419 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-0.71
Solubility :	35.1 mg/ml ; 0.195 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	1.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.81

Safety of [ 331-39-5 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335-H351-H361	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 331-39-5 ]

* 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 [ 331-39-5 ]
Downstream synthetic route of [ 331-39-5 ]

[ 331-39-5 ] Synthesis Path-Upstream 1~12

1
[ 331-39-5 ]
[ 2316-26-9 ]

Reference： [1] Journal of Enzyme Inhibition and Medicinal Chemistry, 2011, vol. 26, # 4, p. 485 - 497

2
[ 215872-63-2 ]
[ 1135-24-6 ]
[ 621-54-5 ]
[ 1135-23-5 ]
[ 331-39-5 ]
[ 102-32-9 ]
[ 306-08-1 ]
[ 1078-61-1 ]
[ 1081-71-6 ]

Reference： [1] Journal of Agricultural and Food Chemistry, 2009, vol. 57, # 8, p. 3356 - 3362

3
[ 215872-63-2 ]
[ 1135-24-6 ]
[ 621-54-5 ]
[ 1135-23-5 ]
[ 331-39-5 ]
[ 102-32-9 ]
[ 306-08-1 ]
[ 1078-61-1 ]
[ 23028-17-3 ]
[ 2475-56-1 ]
[ 1081-71-6 ]

Reference： [1] Journal of Agricultural and Food Chemistry, 2009, vol. 57, # 8, p. 3356 - 3362

4
[ 331-39-5 ]
[ 74-88-4 ]
[ 537-73-5 ]

Reference： [1] Yakugaku Zasshi, 1939, vol. 59, p. engl. Ref. S. 261, 264[2] Chem.Abstr., 1940, p. 1006

5
[ 331-39-5 ]
[ 6537-80-0 ]

Reference： [1] Helvetica Chimica Acta, 2002, vol. 85, # 8, p. 2328 - 2334

6
[ 331-39-5 ]
[ 73635-75-3 ]

Reference： [1] Tetrahedron Letters, 2001, vol. 42, # 19, p. 3303 - 3305

7
[ 60-12-8 ]
[ 331-39-5 ]
[ 104594-70-9 ]

Yield	Reaction Conditions	Operation in experiment
48%	With ytterbium(III) triflate In nitromethane at 120℃; for 0.666667 h;	To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 °C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2percent NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1–5 and 8–30.2-Phenethyl (E)-3-(3,4-dihydroxyphenyl) acrylate (1): Whitesolid; yield 758 mg, 48.0percent; m.p. 128–130 °C (lit.20 116–123 °C);IR (KBr) νmax 3480, 3328, 1683, 1601, 1362, 1301, 1279, 1182 cm–1;1H NMR (400 MHz, DMSO-d6) δH 7.46 (1H, d, J = 16 Hz, CH=CHCO),7.34–7.18 (5H, m, C6H5), 7.05 (1H, s, 2‑ArH), 6.99 (1H, d, J = 8.0 Hz,6‑ArH), 6.77 (1H, d, J = 8.0 Hz, 5‑ArH), 6.24 (1H, d, J = 16 Hz,CH=CHCO), 4.32 (2H, t, J = 6.8 Hz, OCH2), 2.94 (2H, t, J = 6.8 Hz,OCH2CH2) ppm; 13C NMR (100 MHz, DMSO-d6) δC 166.4, 148.3,145.4, 145.1, 138.0, 128.8, 128.3, 126.3, 125.4, 121.4, 115.7, 114.7, 113.8,64.3, 34.4 ppm; HRMS-ESI C17H16O4 calcd [M–H]– 283.0970, found283.0966.
48%	With ytterbium(III) triflate In nitromethane at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH₃NO₂ (125 mL) was added Yb(OTf)₃ (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 °C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2percent NaHCO₃ (30 mL) and brine, dried over anhydrous Na₂SO₄, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61percent yields. Phenethyl (E)-3-(3,4-dihydroxyphenyl) acrylate (CAPE). White solid (48percent yield for esterification reaction); Mp 128–130 °C; ¹H NMR (400 MHz, DMSO-d₆) δ_H 7.46 (1H, d, J = 16.0 Hz, CH=CHCO), 7.34-7.18 (5H, m, C₆H₅), 7.05 (1H, s, 2-ArH), 6.99 (1H, d, J = 8.0 Hz, 5-ArH), 6.77 (1H, d, J = 8.0 Hz, 6-ArH), 6.24 (1H, d, J = 16.0 Hz, CH=CHCO), 4.32 (2H, t, J = 6.8 Hz, OCH₂), 2.94 (2H, t, J = 6.8 Hz, CH₂C₆H₅) ppm; ¹³C NMR (100 MHz, DMSO-d₆) δ_C 166.4, 148.3, 145.4, 145.1, 138.0, 128.8, 128.3, 126.3, 125.4, 121.4, 115.7, 114.7, 113.8, 64.3, 34.4 ppm; HRMS-ESI C₁₇H₁₆O₄ calcd [M-H]^- 283.0970, found 283.0966.

Reference： [1] Patent: EP1211237, 2002, A1, . Location in patent: Example 1
[2] Organic Letters, 2002, vol. 4, # 22, p. 3839 - 3841
[3] Journal of Chemical Research, 2014, vol. 38, # 11, p. 695 - 700
[4] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 2, p. 131 - 134
[5] Patent: EP1211237, 2002, A1, . Location in patent: Page 5
[6] Patent: EP1211237, 2002, A1, . Location in patent: Page 5
[7] Journal of Medicinal Chemistry, 1995, vol. 38, # 21, p. 4171 - 4178
[8] Patent: US5610185, 1997, A,
[9] Chemical and Pharmaceutical Bulletin, 2017, vol. 65, # 11, p. 1020 - 1027

8
[ 331-39-5 ]
[ 103-63-9 ]
[ 104594-70-9 ]

Reference： [1] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 2, p. 236 - 238
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 16, p. 7584 - 7597
[3] Bioorganic and Medicinal Chemistry, 2001, vol. 9, # 1, p. 199 - 209

9
[ 331-39-5 ]
[ 104594-70-9 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 10, p. 3351 - 3359
[2] European Journal of Medicinal Chemistry, 2014, vol. 75, p. 391 - 402

10
[ 60-12-8 ]
[ 331-39-5 ]
[ 104594-70-9 ]

Reference： [1] Russian Journal of Bioorganic Chemistry, 1995, vol. 21, # 2, p. 124 - 131[2] Bioorganicheskaya Khimiya, 1995, vol. 21, # 2, p. 143 - 151

11
[ 331-39-5 ]
[ 538-75-0 ]
[ 104594-70-9 ]

Reference： [1] Russian Journal of Bioorganic Chemistry, 1995, vol. 21, # 2, p. 124 - 131[2] Bioorganicheskaya Khimiya, 1995, vol. 21, # 2, p. 143 - 151

12
[ 1049703-62-9 ]
[ 331-39-5 ]
[ 77-95-2 ]
[ 2450-53-5 ]

Reference： [1] Agricultural and Biological Chemistry, 1985, vol. 49, # 8, p. 2467 - 2470

[ 331-39-5 ] Synthesis Path-Downstream 1~88

1
[ 331-39-5 ]
[ 74-88-4 ]
[ 537-73-5 ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1939,vol. 59,p. engl. Ref. S. 261, 264
Chem.Abstr.,1940,p. 1006

2
[ 104777-68-6 ]
[ 331-39-5 ]

Reference： [1]Phytochemistry,1986,vol. 25,p. 1633 - 1636

3
[ 122412-14-0 ]
[ 331-39-5 ]
[ 970-73-0 ]

Reference： [1]Chemical and pharmaceutical bulletin,1989,vol. 37,p. 77 - 85

4
[ 619-60-3 ]
[ 228270-44-8 ]
[ 331-39-5 ]
[ 54737-34-7 ]

Reference： [1]Journal of Physical Chemistry,1982,vol. 86,p. 3661 - 3667

5
[ 331-39-5 ]
[ 54737-34-7 ]
[ 619-60-3 ]
[ 228270-44-8 ]

Reference： [1]Journal of Physical Chemistry,1982,vol. 86,p. 3661 - 3667
[2]Journal of Physical Chemistry,1982,vol. 86,p. 3661 - 3667

6
[ 60-12-8 ]
[ 331-39-5 ]
[ 104594-70-9 ]
N,N'-dicyclohexyl-O-(3,4-dihydrocinnamoyl)isourea [ No CAS ]

Reference： [1]Russian Journal of Bioorganic Chemistry,1995,vol. 21,p. 124 - 131
Bioorganicheskaya Khimiya,1995,vol. 21,p. 143 - 151

7
[ 331-39-5 ]
[ 538-75-0 ]
[ 104594-70-9 ]
N,N'-dicyclohexyl-O-(3,4-dihydrocinnamoyl)isourea [ No CAS ]

Reference： [1]Russian Journal of Bioorganic Chemistry,1995,vol. 21,p. 124 - 131
Bioorganicheskaya Khimiya,1995,vol. 21,p. 143 - 151

8
[ 60-12-8 ]
[ 331-39-5 ]
[ 104594-70-9 ]

Yield	Reaction Conditions	Operation in experiment
48%	With ytterbium(III) triflate; In nitromethane; at 120℃; for 0.666667h;Catalytic behavior;	To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2% NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1-5 and 8-30.2-Phenethyl (E)-3-(3,4-dihydroxyphenyl) acrylate (1): Whitesolid; yield 758 mg, 48.0%; m.p. 128-130 C (lit.20 116-123 C);IR (KBr) numax 3480, 3328, 1683, 1601, 1362, 1301, 1279, 1182 cm-1;1H NMR (400 MHz, DMSO-d6) deltaH 7.46 (1H, d, J = 16 Hz, CH=CHCO),7.34-7.18 (5H, m, C6H5), 7.05 (1H, s, 2-ArH), 6.99 (1H, d, J = 8.0 Hz,6-ArH), 6.77 (1H, d, J = 8.0 Hz, 5-ArH), 6.24 (1H, d, J = 16 Hz,CH=CHCO), 4.32 (2H, t, J = 6.8 Hz, OCH2), 2.94 (2H, t, J = 6.8 Hz,OCH2CH2) ppm; 13C NMR (100 MHz, DMSO-d6) deltaC 166.4, 148.3,145.4, 145.1, 138.0, 128.8, 128.3, 126.3, 125.4, 121.4, 115.7, 114.7, 113.8,64.3, 34.4 ppm; HRMS-ESI C17H16O4 calcd [M-H]- 283.0970, found283.0966.
48%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields. Phenethyl (E)-3-(3,4-dihydroxyphenyl) acrylate (CAPE). White solid (48% yield for esterification reaction); Mp 128-130 C; 1H NMR (400 MHz, DMSO-d6) deltaH 7.46 (1H, d, J = 16.0 Hz, CH=CHCO), 7.34-7.18 (5H, m, C6H5), 7.05 (1H, s, 2-ArH), 6.99 (1H, d, J = 8.0 Hz, 5-ArH), 6.77 (1H, d, J = 8.0 Hz, 6-ArH), 6.24 (1H, d, J = 16.0 Hz, CH=CHCO), 4.32 (2H, t, J = 6.8 Hz, OCH2), 2.94 (2H, t, J = 6.8 Hz, CH2C6H5) ppm; 13C NMR (100 MHz, DMSO-d6) deltaC 166.4, 148.3, 145.4, 145.1, 138.0, 128.8, 128.3, 126.3, 125.4, 121.4, 115.7, 114.7, 113.8, 64.3, 34.4 ppm; HRMS-ESI C17H16O4 calcd [M-H]- 283.0970, found 283.0966.
9%	With ytterbium(III) triflate; In nitromethane; for 1.5h;Reflux;	Caffeic acid (0.5 g, 2.78 mmol) and 2-phenylethanol (0.35 mL,2.78 mmol) were dissolved in nitromethane (62.5 mL). Yb(OTf)3(0.017 g, 0.028 mmol) was added, and the suspension was stirredfor 5 min in an ultrasonic bath followed by an additional 1.5 hstirring under reflux [4]. The reaction mixture was stirred at roomtemperature overnight and washed with NaHCO3-solution (2%,15 mL) and brine (15 mL). The organic phase was dried over Na2SO4and concentrated under reduced pressure. The crude product waspurified by column chromatography (silica gel; chloroform/methanol,99:1), and compound 17 was obtained as a white solid (0.07 g,9%); RF 0.04 (silica gel; chloroform/methanol, 99:1); m.p.128-130 C (lit.: [19]: 126-128 C); IR (KBr): nu 3480s, 1685m,1636m, 1602s, 1535w, 1442w, 1363w, 1302m, 1279s, 1182s cm1;UV-vis (CHCl3): lambda (log epsilon) 250 (4.06), 320 (4.21), 353 (4.28) nm; 1HNMR (500 MHz, CDCl3): delta 7.56 (d, J 15.9 Hz, 1H, 3-H), 7.34-7.30(m, 2H, 2-H), 7.27-7.22 (m, 3H, 3-H4-H), 7.07 (d, J 2.0 Hz, 1H, 50-H), 7.01 (dd, J 8.2, 2.0 Hz, 1H, 20-H), 6.87 (d, J 8.2 Hz, 1H, 60-H),6.25 (d, J 15.9 Hz, 1H, 2-H), 4.42 (t, J 7.1 Hz, 2H, 1-H), 3.01 (t,J 7.1 Hz, 2H, 2-H); 13C NMR (125 MHz, CDCl3): delta 167.8 (C-1),146.5 (C-40), 145.2 (C-30), 143.9 (C-3), 138.0 (C-1), 129.1 (C-3), 128.7(C-2), 127.7 (C-10), 126.8 (C-4), 122.7 (C-60), 115.7 (C-2), 115.6 (C-50),144.6 (C-20), 65.3 (C-1), 35.4 (C-2) ppm; MS (ESI, MeOH): m/z(%) 285.0 ([MH], 45), 302.2 ([MNH4], 23), 307.1 ([MNa],100), 446.1 ([3 MKH]2, 44), 580.1 ([4 MNaH]2, 23), 588.0([4MKH]2, 50), 590.8 ([2MNa], 42), 599.9 ([4MZn]2, 48);analysis calcd for C17H16O4 (284.31): C 71.82, H 5.67; found: C 71.69,H 5.83.

	With toluene-4-sulfonic acid; In benzene;	Synthesis of Cinnamic Acid Analogues. The synthesis of cinnamic acid analogues was achieved by straight forward application of literature techniques. Two general approaches, designated "method A" and "method B" were utilized: Method A: Synthesis of Caffeic acid beta-phenylethyl ester (CAPE, 67H-42-A). A solution of 1.80 g (10.0 mmol) of caffeic acid, 17.9 mL (150 mmol) of beta-phenylethyl alcohol and 100 mg of p-toluenesulfonic acid in benzene (100 mL) were stirred overnight at reflux with a Dean Stark trap. Solvent and excess alcohol were removed by distillation and residue purified by silica gel chromatography (petroleum ether/CHCl3). Product was crystallized (ether/petroleum ether) to provide 67H-42-A as snow-white crystals, 1.0 g (35%): mp 128.0 C. 126-128 C.) (Grunberger, D. et al., Experimentia, (1988) 44:230-2).
	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 48h;	General procedure: Cinnamicacid esters (13-22) were synthesized according to a modified previous procedure.31) To a mixture of cinnamic acid derivatives (Ia-d, 3.0 mmol) and the appropriate alcohol (2.0 mmol)in dry tetrahydrofuran (6mL) were added triphenylphosphine (3.0 mmol) and diisopropyl azodicarboxylate (DIAD(3.0mmol). The reaction mixture was stirred for 48h at room temperature and the whole mixture was extracted with AcOEt and saturated NaHCO3 solution, and the organic extract was washed with brine.The organic layer was dried overNa2SO4 and the solvent was evaporated under reduced pressure. The residue was then purified by silica gel column chromatography (hexane:AcOEt=2:1)to give the title compound.

Reference： [1]Patent: EP1211237,2002,A1 .Location in patent: Example 1
[2]Organic Letters,2002,vol. 4,p. 3839 - 3841
[3]Journal of Chemical Research,2014,vol. 38,p. 695 - 700
[4]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134
[5]Patent: EP1211237,2002,A1 .Location in patent: Page 5
[6]Patent: EP1211237,2002,A1 .Location in patent: Page 5
[7]Journal of Medicinal Chemistry,1995,vol. 38,p. 4171 - 4178
[8]European Journal of Medicinal Chemistry,2019,vol. 177,p. 259 - 268
[9]Patent: US5610185,1997,A
[10]Chemical and Pharmaceutical Bulletin,2017,vol. 65,p. 1020 - 1027
[11]Journal of Agricultural and Food Chemistry,2019,vol. 67,p. 2028 - 2035

9
[ 331-39-5 ]
[ 85-61-0 ]
caffeoyl CoA [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With recombinant Selaginella moellendorffii 4-coumarate:coenzyme A ligase 1; ATP; magnesium chloride; In aq. buffer; at 30℃; for 0.5h;pH 7.5;Enzymatic reaction;Kinetics;	General procedure: We performed Sm4CLs enzyme assays to detect the formation of the <strong>[85-61-0]CoA</strong> esters of variouscinnamic acid derivatives. Each 200 muL assay contained 10 mug purified protein, 200 muMsubstrate, 5mMATP, 300 muM<strong>[85-61-0]CoA</strong>, and 5mMMgCl2, made up in 200mMTris-HCl buffer (pH 7.5). Enzymatic reactionswere incubated for 30 min at 30 C, and the reaction products were analyzed using a HPLC device(1260 Infinity Binary LC system, Agilent, Santa Clara, CA, USA), equipped with a multi wavelengthdetector. The samples were separated through a 5-mum reverse-phase XDB-C18 column with a flow rateof 1 mL/min. A linear gradient of solvent A (1% H3PO4 in H2O) and solvent B (CH3CN) were appliedas follows: 0-5 min, 5% B isocratic; 5-35 min, 5-25% B linear; 35-36 min, 25-100% B linear. Standardsolutions of reference compounds were used for calibration.The effects of pH and temperature on the enzyme activity were examined using p-coumaricacid as substrate. To determine optimal pH, enzymatic activity was assessed in 200 mM Tris-HClbuffer (pH 5.0, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, and 9.0), while the optimal temperature was determined bymeasuring enzymatic activity at 10, 20, 30, 40, 50, and 60 C. All experiments were performed intriplicate. Kinetic parameters were determined using different substrate concentrations. We performedthis experiment in triplicate, with 3 mug purified enzyme in a final volume of 200 muL of 200 mM Tris-HClbuffer at the optimal pH and temperature for 10 min. The level of UV absorption was recorded at1 min intervals. Relevant wavelengths were 311 nm (cinnamoyl <strong>[85-61-0]CoA</strong>), 333 nm (p-coumaroyl <strong>[85-61-0]CoA</strong>),346 nm (caffeoyl <strong>[85-61-0]CoA</strong>), 346 nm (feruloyl <strong>[85-61-0]CoA</strong>), and 352 nm (sinapoyl <strong>[85-61-0]CoA</strong>) [37,41,42]. For determiningkinetic properties with dihydro-p-coumaric acid, reactions were incubated at optimal temperature for10 min and analyzed using HPLC, and then the quantity of the reaction product present was estimatedfrom a standard calibration curve.

Reference： [1]Phytochemistry,1997,vol. 44,p. 605 - 608
[2]Phytochemistry,1997,vol. 44,p. 605 - 608
[3]PLoS ONE,2016,vol. 11
[4]Molecules,2018,vol. 23

10
[ 331-39-5 ]
[ 1421-65-4 ]
[ 53755-02-5 ]

Reference： [1]Phytochemistry,2000,vol. 54,p. 387 - 392

11
[ 331-39-5 ]
[ 3417-91-2 ]
2-[3-(3,4-dihydroxy-phenyl)-acryloylamino]-3-(4-hydroxy-phenyl)propionic acid [ No CAS ]

Reference： [1]Phytochemistry,2000,vol. 54,p. 387 - 392

12
[ 331-39-5 ]
[ 103-63-9 ]
[ 104594-70-9 ]

Yield	Reaction Conditions	Operation in experiment
67%		General procedure: To a stirredsolution of the acid (1 mmol) in dry hexamethyl phosphoramide (5 mL), Nua2CO3 (126 mg, 1.19 mmol) wasadded and stirring continued for 30 min. At the end of this period, thecorresponding bromide (1.14 mmol) was added to the reaction mixture followed bya catalytic amount of potassium iodide. The mixture was stirred at room temperaturefor 48 h, after which EtOAc (30 ml) and HCl 0.5 N (5 mL) were added. Theorganic phase was washed with brine, dried over Na2SO4,filtered and concentrated under reduced pressure. The crude product waspurified by column chromatography.

Reference： [1]Chemical and Pharmaceutical Bulletin,2001,vol. 49,p. 236 - 238
[2]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 1085 - 1089
[3]Journal of Medicinal Chemistry,2016,vol. 59,p. 7584 - 7597
[4]Bioorganic and Medicinal Chemistry,2001,vol. 9,p. 199 - 209

13
[ 331-39-5 ]
[ 621-54-5 ]
[ 1078-61-1 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2001,vol. 49,p. 1640 - 1643

14
7-O-[6'-O-(3'',4''-dihydroxycinnamoyl)-β-D-glucopyranosyl]-8-hydroxycoumarin [ No CAS ]
[ 331-39-5 ]
[ 486-35-1 ]

Reference： [1]Phytochemistry,2002,vol. 59,p. 447 - 450

15
1'-O-((E)-3-O-β-D-glucopyranosyl-caffeoyl) α-L-xylopyranosyl-(4''-2')-β-D-glucopyranoside [ No CAS ]
[ 609-06-3 ]
[ 50-99-7 ]
[ 331-39-5 ]

Reference： [1]Phytochemistry,2005,vol. 66,p. 1927 - 1932

16
[ 331-39-5 ]
[ 1421-65-4 ]
[ 120094-83-9 ]

Yield	Reaction Conditions	Operation in experiment
40%		Caffeic acid (140.7 mg, 0.78 mmol) was dissolved in CH2Cl2/DMF (1:3, 3.0 mL), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide(EDC) (247 mL, 147 mmol) and 1-hydroxy-benzotriazole(HOBt) (75.4 mg, 0.56 mmol) were added to the solution. After themixture was cooled in an ice-water bath for 15 min, Et3N (156 mL,1.12 mmol) and compound a (138.3 mg, 0.56 mmol) were added tothe mixture. After stirring at room temperature for 19 h, the mixturewas poured into H2O (50 mL), extracted with EtOAc (50 mL 3), washed with 5% NaHCO3 (150 mL) and brine (150 mL), driedover MgSO4, filtered, and the solvent removed in vacuo. The residue was purified by silica gel column chromatography (CHCl3:MeOH =9:1) to afford clovamide methyl ester (clovamide-Me, 10, 84.7 mg,40%) as a yellow powder: 1H NMR (CD3OD) d 7.36 (1H, d, J = 15.7Hz, H-70), 6.99 (1H, d, J = 1.9 Hz, H-2), 6.89 (1H, dd, J = 8.2, 1.9 Hz,H-6), 6.75 (1H, d, J = 8.2 Hz, H-5), 6.64 (1H, d, J = 1.9 Hz, H-20),6.67 (1H, d, J = 8.1 Hz, H-50), 6.53 (1H, dd, J = 8.1, 1.9 Hz, H-60),6.41 (1H, d, J = 15.7 Hz, H-80), 4.69 (1H, m, H-8), 3.68 (3H, s,MeO-90), 3.02 (1H, dd, J = 13.9, 5.9 Hz, H-7a), 2.93 (1H, dd, J =13.9, 6.6 Hz, H-7b); 13C NMR (CD3OD) d 174.6 (C, C-9), 169.8(C, C-90), 149.5 (C, C-40), 147.3 (C, C-30), 146.8 (C, C-3), 145.9(C, C-4), 143.8 (CH, C-70), 130.2 (C, C-1), 128.9 (C, C-10), 123.1(CH, C-60), 122.4 (CH, C-6), 118.4 (CH, C-80), 118.0 (CH, C-2),117.2 (CH, C-5), 117.1 (CH, C-50), 115.9 (CH, C-20), 56.5 (CH, C-8),53.4 (CH3, CO-9) 39.1 (C, C-7); UV kmax (MeOH) nm (e): 208(12400), 220 (12100), 291 (9700), 324 (10700); HR-ESI-MS (negativeion) m/z: 372.1100 [MH] (calcd for C19H18NO7, 372.1083);[a]D20 +20 (c = 1.0, MeOH).
33.2%		General procedure: To a solution of the corresponding substitutedacid (1 eq, 2.02 mmol) in dichloromethane-N,N-dimethylformamide(DMF) (3 : 1, 20 mL) was added 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) (1 eq, 2.02 mmol),N,N-diisopropylethylamine (DIEA) (1 eq, 2.02 mmol) andN-hydroxybenzotriazole (HOBt) (1 eq, 2.02 mmol). After themixture was stirred at room temperature for 30 min, correspondingamine (1 eq, 2.02 mmol) and triethylammoniumacetate (TEA) (3 eq, 6.06 mmol) was added. The solution wasstirred at room temperature for 4 h and then extracted withdichloromethane. The organic layer was washed with 1 N HClsolution, saturated NaHCO3 solution, water and brine, driedover Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel column chromatography (ethylacetate-hexane, 1 : 2) to obtain the title compound.
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃;	General procedure: As shown in Scheme 1, the synthetic route of the analogues (1-7) involved a two-step sequence viamethyl esterification of L-amino acidand amide condensation. 100 muL SOCl2was added in portions to 4 mL methanol at -10 C,then 1 mmol L-amino acid was addedand the mixture was warmed to room temperature and stirred overnight. After thesolvent was removed, 5 mL CH3CN, 500 muL DIPEA (N,N-Diisopropyl ethylamine), 1.1 mmolcorresponding substituted acid and 1.1 mmol HBTU (O-Benzotriazole-N,N,N',N'-tetramethyl-uronium-hexafluorophosphate)was added into the residue. The mixture was stirred for 1 h at room temperatureto finish condensation. The reaction solution was added 20 mL 1 M HCl, andextracted with ethyl acetate (4 × 20 mL). The combined organic phasewas dried over anhydrous Na2SO4 and finally evaporated invacuum. The residue was purified by silica-gel chromatography using mixtures ofPE/EtOAcas eluent to afford compounds 1-7.At this stage, all compounds were fully analyzed and characterized by nuclearmagnetic resonance (NMR), high resolution massspectrum (HRMS).

Reference： [1]European Journal of Medicinal Chemistry,2007,vol. 42,p. 1309 - 1315
[2]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 3202 - 3209
[3]Biological and Pharmaceutical Bulletin,2017,vol. 40,p. 1475 - 1482
[4]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 302 - 312

17
[ 331-39-5 ]
[ 104594-70-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2002,vol. 10,p. 3351 - 3359
[2]European Journal of Medicinal Chemistry,2014,vol. 75,p. 391 - 402

18
[ 331-39-5 ]
[ 6537-80-0 ]

Reference： [1]Helvetica Chimica Acta,2002,vol. 85,p. 2328 - 2334

19
[ 331-39-5 ]
[ 20283-92-5 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1991,vol. 110,p. 199 - 205

20
[ 331-39-5 ]
[ 3728-20-9 ]
[ 618460-85-8 ]

Reference： [1]Patent: JP2005/522523,2005,A .Location in patent: Page/Page column 33

21
[ 1135-24-6 ]
[ 140-10-3 ]
[ 331-39-5 ]
[ 7400-08-0 ]
[ 6099-04-3 ]
[ 537-73-5 ]
[ 20329-98-0 ]
[ 530-59-6 ]
[ 174472-00-5 ]
[ 640234-76-0 ]
[ 640234-75-9 ]
3-(4-hydroxy-3-(S)-methoxy-phenyl)-N-[2-(4-hydroxy-phenyl)-2-methoxy-ethyl]acrylamide [ No CAS ]
(E)-N-((S)-2-Methoxy-2-phenyl-ethyl)-3-phenyl-acrylamide [ No CAS ]
(E)-3-(3-Methoxy-phenyl)-N-((S)-2-methoxy-2-phenyl-ethyl)-acrylamide [ No CAS ]
(E)-3-(4-Hydroxy-phenyl)-N-((S)-2-methoxy-2-phenyl-ethyl)-acrylamide [ No CAS ]
(-)-aegeline O-methylether [ No CAS ]
(S)-N-(2-(4-hydroxyphenyl)-2-methoxyethyl)cinnamamide [ No CAS ]
(E)-3-(3-Hydroxy-4-methoxy-phenyl)-N-((S)-2-methoxy-2-phenyl-ethyl)-acrylamide [ No CAS ]
3-(4-hydroxyphenyl)-N-[2-(4-hydroxyphenyl)-2-methoxyethyl]acrylamide [ No CAS ]
(E)-N-[(S)-2-(4-Hydroxy-phenyl)-2-methoxy-ethyl]-3-(3-methoxy-phenyl)-acrylamide [ No CAS ]
(E)-3-(3,4-Dihydroxy-phenyl)-N-((S)-2-methoxy-2-phenyl-ethyl)-acrylamide [ No CAS ]
(E)-3-(4-Hydroxy-phenyl)-N-[(S)-2-methoxy-2-(4-methoxy-phenyl)-ethyl]-acrylamide [ No CAS ]
(E)-N-[(S)-2-Methoxy-2-(4-methoxy-phenyl)-ethyl]-3-(3-methoxy-phenyl)-acrylamide [ No CAS ]
(E)-3-(4-Hydroxy-3-methoxy-phenyl)-N-((S)-2-methoxy-2-phenyl-ethyl)-acrylamide [ No CAS ]
(S)-N-[2-(4-methoxyphenyl)-2-methoxyethyl]-3-(4-hydroxy-3-methoxyphenyl)acrylamide [ No CAS ]
(E)-3-(4-Hydroxy-3,5-dimethoxy-phenyl)-N-((S)-2-methoxy-2-phenyl-ethyl)-acrylamide [ No CAS ]
(E)-N-((S)-2-Methoxy-2-phenyl-ethyl)-3-(3,4,5-trimethoxy-phenyl)-acrylamide [ No CAS ]
(E)-3-(3-Hydroxy-4-methoxy-phenyl)-N-[(S)-2-methoxy-2-(4-methoxy-phenyl)-ethyl]-acrylamide [ No CAS ]
(E)-3-(3,4-Dihydroxy-phenyl)-N-[(S)-2-methoxy-2-(4-methoxy-phenyl)-ethyl]-acrylamide [ No CAS ]
(E)-3-(3-Hydroxy-4-methoxy-phenyl)-N-[(S)-2-(4-hydroxy-phenyl)-2-methoxy-ethyl]-acrylamide [ No CAS ]
(E)-3-(3,4-Dihydroxy-phenyl)-N-[(S)-2-(4-hydroxy-phenyl)-2-methoxy-ethyl]-acrylamide [ No CAS ]
(E)-N-[(S)-2-Methoxy-2-(4-methoxy-phenyl)-ethyl]-3-(3,4,5-trimethoxy-phenyl)-acrylamide [ No CAS ]
(E)-3-(4-Hydroxy-3,5-dimethoxy-phenyl)-N-[(S)-2-methoxy-2-(4-methoxy-phenyl)-ethyl]-acrylamide [ No CAS ]
(E)-N-[(S)-2-(4-Hydroxy-phenyl)-2-methoxy-ethyl]-3-(3,4,5-trimethoxy-phenyl)-acrylamide [ No CAS ]
(E)-3-(4-Hydroxy-3,5-dimethoxy-phenyl)-N-[(S)-2-(4-hydroxy-phenyl)-2-methoxy-ethyl]-acrylamide [ No CAS ]

Reference： [1]Patent: WO2005/44191,2005,A2 .Location in patent: Page/Page column 24; 25

22
[ 699-12-7 ]
[ 331-39-5 ]
3,4-dihydroxy-cinnamic acid-(2-thiolphenoxy-ethyl ester) [ No CAS ]

Reference： [1]Journal of the Chinese Chemical Society,2008,vol. 55,p. 698 - 703

23
[ 64-17-5 ]
[ 331-39-5 ]
[ 66648-50-8 ]

Yield	Reaction Conditions	Operation in experiment
Ca. 100%	at 50.0℃; for 48.0h;	General procedure: As a resin that is a solid catalyst, PK208LH manufactured by Mitsubishi Chemical Corporation was used. In this system, conditions without using a solvent were adopted, and therefore, a homogeneous phase was formed by setting the reaction temperature to 50 C. so as to dissolve a cinnamic acid (1) and an alcohol (2). Here, ferulic acid was used as the cinnamic acid, and methanol (MeOH) was used as the alcohol (2), and these components were mixed by setting the cinnamic acid (1): the alcohol (2) to 1:20 (molar ratio). Incidentally, the resin is of H+ type (?99 mol %) showing a catalytic activity, however, it is in a swollen state with water that is a reaction by-product of esterification at the time of factory shipment, and therefore, it was swollen with the alcohol that is a reactant, and thereafter used in the experiment. The swelling was performed by packing the resin in a glass column with an inner diameter of 11 mm and allowing the alcohol (2) to pass through the column at 2.5 cm/min until the water content of the washing liquid was decreased to less than 10 mass %.In this experiment (batch type), 20 g of the reaction solution obtained by homogeneously dissolving by preheating in advance so that the reaction temperature was 50 C. was placed in a glass reactor, and the resin in an alcohol-swollen state preheated in the same manner was fed thereto in an amount of 33 mass % with respect to the total reaction system, followed by shaking at a stirring rate of 150 spm. During the reaction, a small amount was collected from the reaction solution at predetermined time intervals and appropriately diluted with methanol, and the yield of the reaction was traced and determined using an HPLC (Waters Corp., Milford, Mass., USA) system. The yield when the reaction time was 12 hours was 100% (conversion rate: 100%).
81%	With sulfuric acid; for 2.0h;Reflux;	General procedure: Caffeic acid (0.5 g, 2.77 mmol) was dissolved in dry appropriate aliphatic alcohol (20 mL) and H2SO4 (0.5 mL, 96%, v/v) was added. Reaction mixture was reuxed for 2 h. After cooling at room temperature, the solution was diluted with ethyl acetate (100 mL) and washed with an aqueous solution of NaHCO3 (5% w/v) until neutral pH. The organic layer was then washed with distilled water and dried over anhydrous MgSO4, and the solvent was removed under vacuum. The residue was then puried by silica gel circula rchromatography to afford the required ester derivative. 5.1.2.5. Compound 4: procedure 1. Ester 4 (382 mg, 81%) was obtained after silica gel circular chromatography (40% EtOAc-hexane) as a white solid; mp 128-140 C; 1H NMR (400 MHz, DMSO-d6, 25 C) delta (ppm): 9.58 (br s, 1H, OH), 9.14 (br s, 1H, OH), 7.47 (d, J = 15.93 Hz, 1H, CHCar), 7.05 (s, 1H, Har), 7.00 (dd, J = 8.24, 1.16 Hz, 1H, Har), 6.76 (d, J = 8.12 Hz, 1H, Har), 6.26 (d, J = 15.89 Hz, 1H, CHCO), 4.16 (q, J = 7.04 Hz, 2H, CH2CH3), 1.24 (t, J = 7.08 Hz, 3H, CH2CH3); 13C NMR (101 MHz, DMSO-d6, 25 C) delta (ppm): 167.01, 148.83, 146.02, 145.45, 125.97, 121.80, 116.19, 115.26, 114.51, 60.15, 14.73; HRMS m/z calcd for C10H12O4+(H+): 209.0808; found: 209.0811.
	With sulfuric acid; at 100.0℃; for 0.116667h;Microwave irradiation;	General procedure: Briefly, the acid (2 g) with the appropriate aromatic pattern, ethanol (2.5 mL) and H2SO4 (3 drops) were put together in a glass vial (2-5 mL) sealed with a cap and heated in the MW reactor cavity under mechanical stirring at 100 C for 7 min. After cooling to room temperature, the solvent was removed and the compounds were purified by flash chromatography (silica gel; hexane with increasing ethyl acetate gradient) and recrystallized from diethyl ether/petroleum ether.

	With sulfuric acid;	General procedure: As recently reported (Sanderson et al., 2013), alkyl esters 6-12 were prepared by esterification with selected alcohol and commercially available caffeic acid (4) in the presence of sulfuric acid.
	With sulfuric acid;Reflux;	General procedure: A mixture of caffeic acid (0.25 g, 1.39 mmol) and alcohol (50 ml) was heated under reflux in the presence of sulfuric acid (0.4 ml) until completion of the reaction (5-21 hours)and verified by a single spot in TLC. The alcohol was then removed under reduced pressure, and the solution was diluted with 20 ml of water. The product was extracted with ethyl acetate (15 ml). The organic phase was neutralized successively with 5% sodium bicarbonate and water, dried over anhydrous sodium sulfate, and filtered. After evaporation under reduced pressure, this phase yielded the ester derivatives [44].

Reference： [1]Patent: US2020/123094,2020,A1 .Location in patent: Paragraph 0066-0067; 0072; 0075
[2]Journal of Pharmacy and Pharmacology,2018,vol. 70,p. 1349 - 1356
[3]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 7182 - 7193
[4]Molecules,2010,vol. 15,p. 6152 - 6167
[5]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 6085 - 6088
[6]ChemMedChem,2020,vol. 15,p. 68 - 78
[7]Journal of Agricultural and Food Chemistry,2008,vol. 56,p. 1376 - 1386
[8]European Journal of Medicinal Chemistry,2009,vol. 44,p. 4596 - 4602
[9]European Journal of Medicinal Chemistry,2013,vol. 62,p. 289 - 296
[10]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 1502 - 1505
[11]European Journal of Pharmacology,2014,vol. 730,p. 125 - 132
[12]RSC Advances,2014,vol. 4,p. 20781 - 20788
[13]Electrochimica Acta,2015,vol. 178,p. 533 - 540
[14]Mediators of Inflammation,2017,vol. 2017
[15]Journal of Chemistry,2019,vol. 2019

24
[ 215872-63-2 ]
[ 1135-24-6 ]
[ 621-54-5 ]
[ 1135-23-5 ]
[ 331-39-5 ]
[ 102-32-9 ]
[ 306-08-1 ]
[ 1078-61-1 ]
[ 23028-17-3 ]
[ 2475-56-1 ]
[ 1081-71-6 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2009,vol. 57,p. 3356 - 3362

25
[ 215872-63-2 ]
[ 1135-24-6 ]
[ 621-54-5 ]
[ 1135-23-5 ]
[ 331-39-5 ]
[ 102-32-9 ]
[ 306-08-1 ]
[ 1078-61-1 ]
[ 1081-71-6 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2009,vol. 57,p. 3356 - 3362

26
[ 20283-92-5 ]
[ 331-39-5 ]
[ 23028-17-3 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2009,vol. 57,p. 7700 - 7705

27
[ 327-97-9 ]
[ 331-39-5 ]
[ 77-95-2 ]

Reference： [1]Chemistry of Natural Compounds,2010,vol. 46,p. 303 - 304
[2]Molecules,2018,vol. 23

28
[ 331-39-5 ]
[ 23028-17-3 ]
C₁₈H₁₈O₉ [ No CAS ]
C₁₈H₁₈O₉ [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2011,vol. 59,p. 88 - 95

29
[ 20283-92-5 ]
C₁₈H₁₈O₉ [ No CAS ]
C₁₈H₁₈O₉ [ No CAS ]
[ 331-39-5 ]
[ 23028-17-3 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2011,vol. 59,p. 88 - 95

30
[ 327-97-9 ]
[ 32719-11-2 ]
[ 1258222-08-0 ]
[ 1258222-09-1 ]
[ 331-39-5 ]
[ 77-95-2 ]
[ 905-99-7 ]
[ 14534-61-3 ]
[ 202650-88-2 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2010,vol. 58,p. 12578 - 12584

31
[ 327-97-9 ]
[ 32719-11-2 ]
[ 1258222-08-0 ]
[ 1258222-09-1 ]
[ 331-39-5 ]
[ 77-95-2 ]
[ 905-99-7 ]
[ 202650-88-2 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2010,vol. 58,p. 12578 - 12584

32
[ 327-97-9 ]
[ 331-39-5 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2011,vol. 59,p. 3812 - 3818

33
[ 20283-92-5 ]
[ 331-39-5 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2011,vol. 59,p. 3812 - 3818

34
[ 2316-26-9 ]
[ 331-39-5 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6183 - 6196

35
[ 331-39-5 ]
[ 491-54-3 ]
[ 1219698-82-4 ]
[ 1219698-83-5 ]

Yield	Reaction Conditions	Operation in experiment
	Laccase DAIWA Y120; In water; at 50℃; for 0.516667h;Enzymatic reaction;	<strong>[491-54-3]Kaempferide</strong> (100 mug) and caffeic acid (100 mug) were dissolved in purified water (200 muL), and the mixture was warmed in an incubator at 50 C. for 1 minute. Laccase DAIWA Y120 (10 muL, Amano Enzyme Inc.) prepared to 5 mg/mL was added and the mixture was stirred for 1 minute. Ethanol (200 muL) was further added to quench the enzyme reaction. This reaction mixture (1 muL) was analyzed by LC/MS, and two components having a molecular weight of 478 could be confirmed in the fractions is with retention time 52.4 minutes and 54.4 minutes. UV spectrum was simultaneously measured by a photodiode array detector (see FIGS. 30 to 32). As a result of the UV spectrum analysis of each component, the absorption around 370 nm derived from ring C of kaempferide disappeared, and only the absorption around 280 nm derived from ring A and ring B was strongly detected, which confirms that the structure of (compound 29) or (compound 30) was produced. The apparatus and measurement conditions of LC/MS and photodiode array detector are shown below.LC/MS analysis apparatus:LC: Waters Alliance 2695detector: Waters 2996 Photodiode array detector (manufactured by Waters)detector: Waters Quattro micro API (manufactured by Waters) ionization method: ESILC/MS analysis conditions:column: CAPCELL PAK AQ S-3 mum, 2×250 mm (manufactured by Shiseido Co., Ltd.)gradient conditions: 0 minute (SOLUTION A/SOLUTION B=100:0), 100 minutes (SOLUTION A/SOLUTION B=0:100), injection volume: 1 muL, flow rate: 0.2 mL/minute, solvent: SOLUTION A solution of 0.05% trifluoroacetic acid and 10% acetonitrile in water, SOLUTION B solution of 0.05% trifluoroacetic acid and 80% acetonitrile in water

Reference： [1]Patent: US2011/237533,2011,A1 .Location in patent: Page/Page column 27

36
[ 67-56-1 ]
[ 327-97-9 ]
[ 3843-74-1 ]
[ 331-39-5 ]

Reference： [1]Journal of Molecular Catalysis B: Enzymatic,2011,vol. 69,p. 161 - 167

37
[ 1124-63-6 ]
[ 327-97-9 ]
[ 331-39-5 ]
[ 1240244-46-5 ]

Reference： [1]Journal of Molecular Catalysis B: Enzymatic,2011,vol. 69,p. 161 - 167

38
[ 331-39-5 ]
[ 2316-26-9 ]

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2011,vol. 26,p. 485 - 497

39
[ 331-39-5 ]
[ 999-81-5 ]
[ 76-05-1 ]
[ 1314894-96-6 ]

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2011,vol. 26,p. 485 - 497

40
[ 20283-92-5 ]
[ 331-39-5 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2012,vol. 60,p. 10320 - 10330

41
[ 331-39-5 ]
[ 139152-08-2 ]
[ 1446888-26-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 48h;Inert atmosphere;	General procedure: Captopril phthalonitrile (4) was synthesized as follows: to dry DMSO (10 ml) under nitrogen atmosphere, captopril (0.8 g, 3.68 mmol) and 4-nitrophthalonitrile (3a, 1 g, 5.78 mmol) were added and the mixture left to stir for 15 min. K2CO3 (2.5 g, 18.09 mmol) was added to the mixture over 2 h. The mixture was stirred for a total of 48 h at room temperature. After 48 h, the product formed was precipitated out by acetone, filtered and air dried.

Reference： [1]Journal of Photochemistry and Photobiology A: Chemistry,2012,vol. 250,p. 18 - 24

42
[ 331-39-5 ]
[ 7315-32-4 ]

Reference： [1]Tetrahedron Asymmetry,2013,vol. 24,p. 285 - 289

43
[ 75-09-2 ]
[ 331-39-5 ]
[ 7315-32-4 ]

Yield	Reaction Conditions	Operation in experiment
61%	With potassium carbonate; In N,N-dimethyl-formamide; for 18h;Reflux;	4.3.1. One-pot two-step reaction. A solution of 3,4-dihydroxycinnamic acid (2 g, 0.011 mol) in DMF (20 mL) was added dropwise to a suspension of CH2Cl2 (1.4 mL, 0.02 mol) and K2CO3 (4 g, 0.028 mol) in DMF (30 mL). The mixture was stirred and heated at reflux for 18 h then cooled and filtered. The filtrate was concentrated, diluted with water, and extracted with ethyl acetate (3 × 100 mL). The filter cake was washed with ethyl acetate (25 mL). The organic layer was washed with 10% NaOH (25 mL), water (25 mL), dried (Na2SO4), and evaporated to afford 1.0 g (61%) of 1 as a yellow oil. 1H NMR (CDCl3, 400 MHz): delta 5.0 (d, J = 10.86 Hz, 1H, CHCH2), 5.5 (d, J = 17.43 Hz, 1H, CHCH2), 5.9 (s, 2H, OCH2O), 6.5 (dd, J = 10.86, 17.43 Hz, 1H, CHCH2), 6.5 (d, J = 8.08 Hz, 1H, Har), 6.75 (dd, J = 1.52, 7.83 Hz, 1H, Har), 6.9 (d, J = 1.52 Hz, 1H, Har). 13C NMR (CDCl3, 100 MHz): 101, 105, 109, 112, 121, 132, 136, 147, 148.

Reference： [1]Tetrahedron Asymmetry,2013,vol. 24,p. 285 - 289

44
[ 331-39-5 ]
[ 557795-19-4 ]
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide caffeate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In methanol; at 25 - 35℃; for 0.25h;	<strong>[557795-19-4]Sunitinib</strong> (1.0g) was suspended in methanol (152 mL), followed by addition of caffeic acid (0.45g) at 25-35C over a period of 15 minutes. After the stipulated time period, methanol was completely distilled off under vacuum below 45C. The residue was treated with acetonitrile (38ml_) and refluxed. The reaction mass was maintained at reflux temperature for 60 minutes. The reaction mass was cooled to 25-35 C for crystallization. The solid obtained was filtered, washed with acetonitrile, suck dried and dried under vacuum at 60C over 4-5 hr period to obtain <strong>[557795-19-4]sunitinib</strong> caffeate.( 1.3 g; yield:89 %) Purity by HPLC: 99.06 %; caffeic acid content: 30.48 % (w/w); TGA: 0.29 %; DSC: 157-163 C; 190-198 C; 211-214 C IR (in cm"1): 3402,3201 ,2980,1668,1627,1574,1525,1480,1443,1382,1355,1328,1293, 1280, 1257,1231,1193,1164,1149,1121,1096,1071 ,1051 ,1034,1014,982, 917,860, 823, 793,773,719,666,608,586. The XRPD is set forth in Figure. 08.

Reference： [1]Patent: WO2013/140232,2013,A1 .Location in patent: Page/Page column 19

45
[ 331-39-5 ]
[ 184475-35-2 ]
2C₂₂H₂₄ClFN₄O₃*C₉H₈O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In ethanol; at 25 - 80℃;	Preparation of <strong>[184475-35-2]Gefitinib</strong>:Caffeic Acid (2:1); 446.9 mg of <strong>[184475-35-2]gefitinib</strong> and 10 ml of ethanol was taken in a RB flask at 25 C. to 30 C. 180 mg of caffeic acid was added at 25 C. to 30 C. The mixture was heated under reflux temperature (75 C.-80 C.) and stirred until a clear solution is obtained. The stiffing was continued under reflux temperature for 2 hours. The solution was cooled to 25 C. to 30 C. and continued stiffing over night (16 hrs). The solution was filtered and washed with chilled ethanol (1 ml). The product obtained was dried at 25 C. under vacuum for 6 hours.Yield: 523 mg (83%).The XRPD is set forth in FIG. 1. The DSC is set forth in FIG. 2. IR (Cm-1): 557, 860, 1115.2, 1231.8, 1282.5, 1326.2, 1427.8, 1441.7, 1473.7, 1500.5, 1534.7, 1578, 1628.6, 2953.8, 3442.4.

Reference： [1]Patent: US2014/31352,2014,A1 .Location in patent: Paragraph 0108; 0109; 0110; 0111; 0112

46
[ 331-39-5 ]
[ 184475-35-2 ]
2C₂₂H₂₄ClFN₄O₃*C₉H₈O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In ethanol; at 25 - 80℃; for 18h;	446.9 mg of <strong>[184475-35-2]gefitinib</strong> and 10 ml of ethanol was taken in a RB flask at 25C to 30C. 180 mg of caffeic acid was added at 25C to 30C. The mixture washeated under reflux temperature (75C - 80C) and stirred until a clear solution isobtained. The stirring was continued under reflux temperature for 2 hours. The solutionwas cooled to 25C to 30C and continued stirring over night (-l6hrs). The solution wasfiltered and washed with chilled ethanol (1 ml). The product obtained was dried at 25Cunder vacuum for 6 hours.[00109] Yield: 523 mg (83%).[00110] The XRPD is set forth in Figure 1.[001111 The DSC is set forth in Figure 2.[001 121 IR (Cm1): 557, 860, 1115.2, 1231.8, 1282.5, 1326.2, 1427.8, 1441.7,1473.7, 1500.5, 1534.7, 1578, 1628.6, 2953.8, 3442.4.

Reference： [1]Patent: WO2014/16848,2014,A2 .Location in patent: Paragraph 00108-00112

47
[ 331-39-5 ]
[ 6305-38-0 ]
C₁₃H₁₃NO₅ [ No CAS ]

Reference： [1]ChemBioChem,2014,vol. 15,p. 87 - 93

48
[ 331-39-5 ]
[ 331-61-3 ]
[ 1580002-51-2 ]

Yield	Reaction Conditions	Operation in experiment
25%		General procedure: In an ice bath, to 1.61 mmol of caffeic acid, dissolved in 2 mL of DMF, 0.4 mL of aqueous 0.4 M NaOH were added. After 20 min, at rt, 1.65 mmol of the opportune bromide were added in small portions over a period of 60 min. The mixture was raised to room temperature and stirred for 50 h. The reaction mixture was poured in 10 mL of water and extracted with ethyl acetate (3 × 20 mL). The combined organic layers were washed with 20 mL of 1 M HCl and water, drying over Na2SO4 and evaporated under reduced pressure. For 6, the crude residue was subjected to silica gel column chromatography using Et2O/n-hexane (80:20 v/v) until the output of the bromide and after Et2O to give 6 as white solid crystallized from AcOEt/petroleum ether (25% yield). For 7 the residue was subjected to silica gel column chromatography using AcOEt-MeOH (95:5 v/v) to give a yellow solid (20% yield).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 1502 - 1505

49
[ 331-39-5 ]
[ 20782-91-6 ]
[ 1580002-52-3 ]

Yield	Reaction Conditions	Operation in experiment
20%		General procedure: In an ice bath, to 1.61 mmol of caffeic acid, dissolved in 2 mL of DMF, 0.4 mL of aqueous 0.4 M NaOH were added. After 20 min, at rt, 1.65 mmol of the opportune bromide were added in small portions over a period of 60 min. The mixture was raised to room temperature and stirred for 50 h. The reaction mixture was poured in 10 mL of water and extracted with ethyl acetate (3 × 20 mL). The combined organic layers were washed with 20 mL of 1 M HCl and water, drying over Na2SO4 and evaporated under reduced pressure. For 6, the crude residue was subjected to silica gel column chromatography using Et2O/n-hexane (80:20 v/v) until the output of the bromide and after Et2O to give 6 as white solid crystallized from AcOEt/petroleum ether (25% yield). For 7 the residue was subjected to silica gel column chromatography using AcOEt-MeOH (95:5 v/v) to give a yellow solid (20% yield).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 1502 - 1505

50
[ 331-39-5 ]
[ 143491-57-0 ]
emtricitabine caffeate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4 g	In methanol; at -5 - 65℃; for 24.5h;	Charged 5 gms of Emtricitabine, 3.64 gms of caffeic acid and 45 ml of methanol in to a round bottom flask at 25 C. to 35 C. and heated to 60 C. to 65 C. to form a clear solution. Then the solution cooled to 0-5 C. and stirred for 30 minutes followed by raised temperature to 25 C. to 30 C. and stirred for 24 hours. The obtained solids were filtered and dried at 60 C. to 65 C. for 3 hours to afford 4 gms of the title compound. [0197] The XRPD is set forth in FIG. 14.

Reference： [1]Patent: US2014/94475,2014,A1 .Location in patent: Paragraph 0195-0197

51
[ 331-39-5 ]
[ 1501-84-4 ]
[ 1656284-97-7 ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: In a typical preparation, to a solution of substituted cinnamic acid (3.2 mmol), EDC(0.61 g, 3.2 mmol) and 1-hydroxybenzotriazole (0.43 g, 3.2 mmol) in 10 mL THF, after 10min stirring at 0 C, the antiviral compound (3.2 mmol) and NMM (0.35 mL, 3.2 mmol),dissolved in 7 mL THF were added. The resultant reaction mixture was stirred for 1 h at 0 Cand then for 24 h at room temperature, under a nitrogen atmosphere. After completion of thereaction (TLC control - CH2Cl2/CH3OH (3:0.2; 3:0.3); CH2Cl2/EtOAc/CH3OH (3:0.1:0.1)),the THF was evaporated in vacuo, and the residue was diluted with EtOAc and then was successivelywashed with 5 % NaHSO4, NaHCO3 and brine, dried over anhydrous Na2SO4 andevaporated in vacuo. The residue was purified by column chromatography or preparative TLCon silica gel (CH2Cl2/CH3OH) to give the desired compound.

Reference： [1]Journal of the Serbian Chemical Society,2014,vol. 79,p. 517 - 526

52
[ 537-73-5 ]
[ 331-39-5 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5333 - 5347

53
3-(6-feruloyl-β-D-glucopyranosyl)rosmarinic acid [ No CAS ]
[ 137887-25-3 ]
[ 331-39-5 ]
[ 23028-17-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water; at 60℃; for 3.0h;	General procedure: Compounds 1 (1mg), 2 (1.5mg), 9 (1.9mg), 14 (2.5mg), 15 (2.0mg), and 17 (7.6mg) were separately hydrolyzed with 2N HCl (0.5mL) at 60C for 3h. Each reaction mixture was neutralized using an Amberlite IRA400 column (Sigma-Aldrich Co. LLC., St. Louis, MO, USA), and each eluate was concentrated. Residues were individually stirred with l-cysteine methyl ester (5mg) and O-tolyl isothiocyanate (20muL) in pyridine (0.5mL), using the procedure reported by Tanaka and colleagues (Tanaka et al., 2007). (0047) Each of the mixtures was analyzed by HPLC (column, Cosmosil 5C18-AR II column, 4.6×250mm, Nacalai tesque; mobile phase, CH3CN-0.2% TFA in H2O (25:75), 1.0mL/min; detector, UV at 210nm) at 20C. d-Glucose (tR 16.4min) was identified as the glycosidic moiety of 1, 2, 9, and 14 in comparison with the authentic samples of d-glucose derivatives (tR 16.4min) and l-glucose derivatives (tR 15.3min). d-Glucuronic acid (tR 16.2min) was identified as the glycosidic moiety of 15 and 17 by comparison with authentic samples of d-glucuronic acid derivatives (tR 16.2min) and l-glucuronic acid derivatives (using d-cysteine methyl ester and d-glucuronide, tR 15.1min).

Reference： [1]Phytochemistry,2014,vol. 101,p. 91 - 100

54
[ 331-39-5 ]
[ 50919-06-7 ]
2-(2-fluorophenyl)ethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48.1%	With ytterbium(III) triflate; In nitromethane; at 120℃; for 0.666667h;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2% NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1-5 and 8-30.
48%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.

Reference： [1]Journal of Chemical Research,2014,vol. 38,p. 695 - 700
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134

55
[ 52059-53-7 ]
[ 331-39-5 ]
2-(3-fluorophenyl)ethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.
52.8%	With ytterbium(III) triflate; In nitromethane; at 120℃; for 0.666667h;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2% NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1-5 and 8-30.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134
[2]Journal of Chemical Research,2014,vol. 38,p. 695 - 700

56
[ 331-39-5 ]
[ 5182-44-5 ]
2-(3-chlorophenyl)ethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47.3%	With ytterbium(III) triflate; In nitromethane; at 120℃; for 0.666667h;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2% NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1-5 and 8-30.
47%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.

Reference： [1]Journal of Chemical Research,2014,vol. 38,p. 695 - 700
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134

57
[ 331-39-5 ]
[ 19819-98-8 ]
2-(2-methylphenyl)ethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.
48.5%	With ytterbium(III) triflate; In nitromethane; at 120℃; for 0.666667h;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2% NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1-5 and 8-30.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134
[2]Journal of Chemical Research,2014,vol. 38,p. 695 - 700

58
[ 331-39-5 ]
[ 1875-89-4 ]
2-(3-methylphenyl)ethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 °C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2percent NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61percent yields.
53.5%	With ytterbium(III) triflate; In nitromethane; at 120℃; for 0.666667h;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 °C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2percent NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1?5 and 8?30.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134
[2]Journal of Chemical Research,2014,vol. 38,p. 695 - 700

59
[ 331-39-5 ]
[ 455-01-6 ]
3’-(trifluoromethyl)phenethyl (E)-3-(3,4-dihydroxy phenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.
51.7%	With ytterbium(III) triflate; In nitromethane; at 120℃; for 0.666667h;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2% NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1-5 and 8-30.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134
[2]Journal of Chemical Research,2014,vol. 38,p. 695 - 700

60
[ 331-39-5 ]
[ 2968-93-6 ]
4’-(trifluoromethyl)phenethyl (E)-3-(3,4-dihydroxy phenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46.3%	With ytterbium(III) triflate; In nitromethane; at 120℃; for 0.666667h;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2% NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1-5 and 8-30.
46%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.

Reference： [1]Journal of Chemical Research,2014,vol. 38,p. 695 - 700
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134

61
[ 100-27-6 ]
[ 331-39-5 ]
2-(4-nitro)phenethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With ytterbium(III) triflate; In nitromethane; at 120℃; for 0.666667h;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2% NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1-5 and 8-30.
53%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.
28%		General procedure: To a mixture of the acid (1 mmol) in 3 mL anhydrous 1,2-dimethoxyethane,thionyl chloride (6 mmol) was added. The mixture was heated to 70oCfor 4 h and then evaporated under vacuum to remove the excess thionyl chloridecompletely. The intermediate was redissolved with 3 mL anhydrous DME, and tothis solution the alcohol (1 mmol) was added. This mixture was heated to 70oCfor 16 h before evaporation. The residue was purified by column chromatographyto give target compounds.

Reference： [1]Journal of Chemical Research,2014,vol. 38,p. 695 - 700
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134
[3]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 1085 - 1089

62
[ 331-39-5 ]
[ 69395-13-7 ]
4'-cyanophenethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.
60.5%	With ytterbium(III) triflate; In nitromethane; at 120℃; for 1.5h;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol, 1.0 equiv.),alcohol (5.56 mmol, 1.0 equiv.) in nitromethane (125 mL) was addedytterbium triflate (34.4 mg, 0.056 mmol, 0.01 equiv.). After 5 min inan ultrasonic bath the mixture without protective gas was stirred ona 120 C oil bath for a given time. The reaction mixture was cooled toroom temperature, washed with deionised water (30 mL), 2% NaHCO3(30 mL) and brine, dried over anhydrous Na2SO4 and evaporated underreduced pressure to give the crude product, which was purified on asilica gel column to give the compounds 1-5 and 8-30.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134
[2]Journal of Chemical Research,2014,vol. 38,p. 695 - 700

63
[ 331-39-5 ]
[ 557795-19-4 ]
sunitinib caffeate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In methanol; at 25 - 35℃; for 0.25h;	Example 10 Preparation of <strong>[557795-19-4]Sunitinib</strong> Caffeate [0151] <strong>[557795-19-4]Sunitinib</strong> (1.0 g) was suspended in methanol (152 mL), followed by addition of caffeic acid (0.45 g) at 25-35 C. over a period of 15 minutes. After the stipulated time period, methanol was completely distilled off under vacuum below 45 C. The residue was treated with acetonitrile (38 mL) and refluxed. The reaction mass was maintained at reflux temperature for 60 minutes. The reaction mass was cooled to 25-35 C. for crystallization. The solid obtained was filtered, washed with acetonitrile, suck dried and dried under vacuum at 60 C. over 4-5 hr period to obtain <strong>[557795-19-4]sunitinib</strong> caffeate. (1.3 g; yield:89%) [0152] Purity by HPLC: 99.06%; caffeic acid content: 30.48% (w/w); [0153] TGA: 0.29%; DSC: 157-163 C.; 190-198 C.; 211-214 C. [0154] IR (in cm-1): 3402, 3201, 2980, 1668, 1627, 1574, 1525, 1480, 1443, 1382, 1355, 1328, 1293, 1280, 1257, 1231, 1193, 1164, 1149, 1121, 1096, 1071, 1051, 1034, 1014, 982, 917, 860, 823, 793, 773, 719, 666, 608, 586. [0155] The XRPD is set forth in FIG. 08.

Reference： [1]Patent: US2015/25252,2015,A1 .Location in patent: Paragraph 0151-0155

64
[ 331-39-5 ]
[ 23593-75-1 ]
C₂₂H₁₇ClN₂*C₉H₈O₄ [ No CAS ]

Reference： [1]Crystal Growth and Design,2015,vol. 15,p. 2493 - 2504

65
[ 331-39-5 ]
[ 128293-62-9 ]
(E)-ethyl 4-(3-(3,4-dihydroxyphenyl)acrylamido)-1-methyl-1H-imidazole-2-carboxylate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 34 - 37

66
[ 331-39-5 ]
[ 304-20-1 ]
E-4-(2-[1,2,4]triazolo[3,4-a]phthalazin-3-yl)vinylbenzene-1,2-diol [ No CAS ]

Reference： [1]ChemMedChem,2016,vol. 11,p. 1078 - 1089

67
[ 331-39-5 ]
[ 5930-28-9 ]
C₁₅H₁₁Cl₂NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%		General procedure: To a well-stirred solution of caffeic acid (1mmol, 180.1 mg) in dry THF, DCC (1.2mmol, 247.5 mg) was added as coupling reagent. After 5 minute individual amine (1.1 mmol) was mixed to each reaction mixture and stirred the reaction mixture for 10-16h under nitrogen atmosphere at room temperature. Individual reaction mixture was filtered and the filtrate was concentrated under vacuum. The concentrated gummy layer was then treated with saturated solution of NaHCO3 and the aqueous layer was neutralized by dilute HCl. The aqueous part was then extracted with ethyl acetate (EtOAc) (3×100 mL). The organic phase was demoisturized with anhydrous sodium sulfate (Na2SO4) and evaporated under reduced pressure. The concentrated organic part was dissolved in acetonitrile (CH3CN) and kept for overnight. Precipitate was observed in each reaction mixture. Individual reaction mixture was filtered and CH3CN layer was concentrated under vacuum. After that, each reaction mixture was purified by flash chromatography using EtOAc and n-hexane as eluent. All compounds were recrystallized by acetone (CH3COCH3) or methanol (MeOH) or ethyl methyl ketone (CH3CH2COCH3) and desire caffeimides were kept in vacuum desiccator until for use. The molecular structures of the compounds (1a-1m) were confirmed by spectroscopic methods.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5943 - 5946

68
[ 331-39-5 ]
[ 1199-46-8 ]
C₁₉H₂₁NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%		General procedure: To a well-stirred solution of caffeic acid (1mmol, 180.1 mg) in dry THF, DCC (1.2mmol, 247.5 mg) was added as coupling reagent. After 5 minute individual amine (1.1 mmol) was mixed to each reaction mixture and stirred the reaction mixture for 10-16h under nitrogen atmosphere at room temperature. Individual reaction mixture was filtered and the filtrate was concentrated under vacuum. The concentrated gummy layer was then treated with saturated solution of NaHCO3 and the aqueous layer was neutralized by dilute HCl. The aqueous part was then extracted with ethyl acetate (EtOAc) (3×100 mL). The organic phase was demoisturized with anhydrous sodium sulfate (Na2SO4) and evaporated under reduced pressure. The concentrated organic part was dissolved in acetonitrile (CH3CN) and kept for overnight. Precipitate was observed in each reaction mixture. Individual reaction mixture was filtered and CH3CN layer was concentrated under vacuum. After that, each reaction mixture was purified by flash chromatography using EtOAc and n-hexane as eluent. All compounds were recrystallized by acetone (CH3COCH3) or methanol (MeOH) or ethyl methyl ketone (CH3CH2COCH3) and desire caffeimides were kept in vacuum desiccator until for use. The molecular structures of the compounds (1a-1m) were confirmed by spectroscopic methods.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5943 - 5946

69
[ 331-39-5 ]
[ 1134-94-7 ]
C₂₁H₁₇NO₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%		General procedure: To a well-stirred solution of caffeic acid (1mmol, 180.1 mg) in dry THF, DCC (1.2mmol, 247.5 mg) was added as coupling reagent. After 5 minute individual amine (1.1 mmol) was mixed to each reaction mixture and stirred the reaction mixture for 10-16h under nitrogen atmosphere at room temperature. Individual reaction mixture was filtered and the filtrate was concentrated under vacuum. The concentrated gummy layer was then treated with saturated solution of NaHCO3 and the aqueous layer was neutralized by dilute HCl. The aqueous part was then extracted with ethyl acetate (EtOAc) (3×100 mL). The organic phase was demoisturized with anhydrous sodium sulfate (Na2SO4) and evaporated under reduced pressure. The concentrated organic part was dissolved in acetonitrile (CH3CN) and kept for overnight. Precipitate was observed in each reaction mixture. Individual reaction mixture was filtered and CH3CN layer was concentrated under vacuum. After that, each reaction mixture was purified by flash chromatography using EtOAc and n-hexane as eluent. All compounds were recrystallized by acetone (CH3COCH3) or methanol (MeOH) or ethyl methyl ketone (CH3CH2COCH3) and desire caffeimides were kept in vacuum desiccator until for use. The molecular structures of the compounds (1a-1m) were confirmed by spectroscopic methods.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5943 - 5946

70
[ 331-39-5 ]
[ 15121-84-3 ]
2'-nitrophenethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 °C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2percent NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61percent yields.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134

71
[ 331-39-5 ]
[ 94022-96-5 ]
2’-(trifluoromethyl)phenethyl (E)-3-(3,4-dihydroxy phenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134

72
[ 331-39-5 ]
[ 7768-28-7 ]
2’-hydroxyphenethyl (E)-3-(3, 4-dihydroxy phenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 °C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2percent NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61percent yields.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134
[2]Journal of Agricultural and Food Chemistry,2019,vol. 67,p. 2028 - 2035

73
[ 7417-18-7 ]
[ 331-39-5 ]
2'-methoxyphenethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134
[2]Journal of Agricultural and Food Chemistry,2019,vol. 67,p. 2028 - 2035

74
[ 331-39-5 ]
[ 52022-77-2 ]
3'-nitrophenethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134

75
[ 331-39-5 ]
[ 193290-27-6 ]
3'-cyanophenethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134

76
[ 331-39-5 ]
[ 22545-12-6 ]
2'-ethylphenethyl (E)-3-(3,4-dihydroxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With ytterbium(III) triflate; In nitromethane; at 120℃;	General procedure: To a mixture of caffeic acid fine powder (1.0 g, 5.56 mmol), various phenethyl alcohols (5.56 mmol) in CH3NO2 (125 mL) was added Yb(OTf)3 (34.4 mg, 0.056 mmol). After 5 min of ultrasonic shake, the mixture was stirred on a 120 C oil bath for 40-120 min. The reaction mixture was cooled to room temperature, washed with 2% NaHCO3 (30 mL) and brine, dried over anhydrous Na2SO4, and concentrated to give crude products, which were purified by column chromatography to give the compounds 1-26 in 18-61% yields.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 131 - 134

77
[ 331-39-5 ]
[ 17585-69-2 ]
(S,E)-2-(3-(3,4-dihydroxyphenyl)acrylamido)-3-phenylpropanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%		1) Weigh caffeic acid 90mg (0.5mmol) was added 10mL round bottom flask, was added dropwise to the round bottom flask 5mL trichloroethane, coffee acid was dissolved;2) A round bottom flask was added 208 L (about 1.5 mmol) of triethylamine, under ice-cooling with stirring 10min, the temperature of the system reached 0 deg.] C;3) with stirring under Yu Bing water bath and a round bottom flask was added EDCI (1- ethyl - (3-dimethylaminopropyl) carbodiimide hydrochloride) 143 mg (0.75 mmol) and DMAP ( 4-dimethylaminopyridine) 91.5mg (0.75mmol), 20min after addition of L- <strong>[17585-69-2]phenylalanine hydrochloride</strong> 101mg (0.5mmol) in a round bottom flask, the temperature was raised to 40 , stirring continued at 24 hours;4) After the reaction was drained under reduced pressure (rotary evaporator, -0.08MPa, 45 ) solvent, ethyl acetate was added 20mL shake, the organic phase is suction filtered, the filtrate was washed successively with upper mass fraction of 5percent aqueous sodium bicarbonate and washed with saturated brine (10mL * 2), dried over anhydrous sodium sulfate, and drained under reduced pressure (rotary evaporator, -0.08MPa, 45 ) solvent to give a pale brown solid crude product (total volume of the solid by column chromatography the crude product was multiple quality: gradient I is 10-fold, 20-fold gradient II, III gradient 5 times) to give the caffeic acid - phenylalanine (73.8 mg, 45percent yield).

Reference： [1]Patent: CN106242987,2016,A .Location in patent: Paragraph 0046-0052

78
[ 331-39-5 ]
[ 100-81-2 ]
(E)-3-(3,4-dihydroxyphenyl)-N-(3-methylbenzyl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67.1%		Caffeic acid (200 mg, 1.11 mmol), HOBt (150 mg, 1.11 mmol) and EDCI (212 mg, 1.11 mmol) were dissolved in DMF (3 mL) and the mixture was stirred at room temperature for 20 minutes. After 20 minutes, 3-methylbenzylamine (0.14 mL, 1.11 mmol) was added and the mixture was stirred at room temperature for 20 minutes. After 20 min DIPEA (0.39 mL, 2.22 mmol) was added and stirred for 16 h, then extracted with EtOAc, water, 1N-HCl and brine. The organic layer was dried over anhydrous Mg2SO4, concentrated under reduced pressure and purified by column chromatography. Yield 67.1%
		General procedure: To a solution of caffeic acid (1.0 equiv.), HOBt (1.0 equiv.) and EDCI (1.0 equiv.) in DMF were stirred at room temperature for 15 min. To this solution was added amine derivative (1.0 equiv.) and the reaction mixture was stirred at room temperature. After 15 min the reaction mixture was treated with DIPEA (2.0 equiv.) stirred at room temperature for 16 h. The reaction progress is monitored by TLC and then it was quenched with 1N HCl and extracted with EtOAc (3 x 15 mL), the organic layer was dried over MgSO4, filtered, concentrated in vacuo. The residue was purified by silica gel column chromatography (10-25% EtOAc/hexanes) to afford desired products in good yields (5-90%).

Reference： [1]Patent: KR101693033,2017,B1 .Location in patent: Paragraph 0308; 0309; 0310; 0311
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3374 - 3377

79
[ 2740-83-2 ]
[ 331-39-5 ]
(E)-3-(3,4-dihydroxyphenyl)-N-(3-(trifluoromethyl)benzyl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.2%		Caffeic acid (200 mg, 1.11 mmol), HOBt (150 mg, 1.11 mmol) and EDCI (212 mg, 1.11 mmol) were dissolved in DMF (3 mL) and the mixture was stirred at room temperature for 20 minutes. After 20 minutes, 3- (trifluoromethyl) benzylamine (0.16 mL, 1.11 mmol) was added and the mixture was stirred at room temperature for 20 minutes. After 20 min DIPEA (0.39 mL, 2.22 mmol) was added and stirred for 16 h, then extracted with EtOAc, water, 1N-HCl and brine. The organic layer was dried over anhydrous Mg2SO4, concentrated under reduced pressure and purified by column chromatography. Yield 80.2%
		General procedure: To a solution of caffeic acid (1.0 equiv.), HOBt (1.0 equiv.) and EDCI (1.0 equiv.) in DMF were stirred at room temperature for 15 min. To this solution was added amine derivative (1.0 equiv.) and the reaction mixture was stirred at room temperature. After 15 min the reaction mixture was treated with DIPEA (2.0 equiv.) stirred at room temperature for 16 h. The reaction progress is monitored by TLC and then it was quenched with 1N HCl and extracted with EtOAc (3 x 15 mL), the organic layer was dried over MgSO4, filtered, concentrated in vacuo. The residue was purified by silica gel column chromatography (10-25% EtOAc/hexanes) to afford desired products in good yields (5-90%).

Reference： [1]Patent: KR101693033,2017,B1 .Location in patent: Paragraph 0282; 0283; 0284; 0285
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3374 - 3377

80
[ 331-39-5 ]
[ 62-31-7 ]
N-caffeoyldopamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; N,N-dimethyl-formamide; at 20℃; for 10h;Inert atmosphere;	To a suspension of 3-Hydroxytyramine Hydrochloride (20a, 284.6 mg, 1.5 mmol) in DMF (500 muL) was added N,N-diisopropylethylamine (226.4 muL, 1.3 mmol), and DMAP (135.6 mg, 1.11 mmol). The mixture was diluted with THF (5 mL) and caffeic acid (180.4 mg, 1.01 mmol) and EDCI (192.6 mg, 1.00 mmol) were then added. The solution was stirred at room temperature for 10 h. The solution was then diluted with AcOEt and washed sequentially with 1 M HCl, sat. NaHCO3, and brine. The organic solution was dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (MeOH-CHCl3) (1:5 v/v) to give a title compound (255.0 mg, 81%) as a white solid. Mp: 86-90 C, IR : 3357, 3111, 2951, 1644, 1601, 1562, 1527, 1440, 1351, 1180, 1051 cm-1. 1H NMR (500 MHz, CD3OD) delta: 7.89 (s, 1H), 7.37 (d, 2H, J = 15.8 Hz), 6.98 (d, 2H, J = 2.0 Hz), 6.88 (dd, 2H, J = 2.0, 8.3 Hz), 6.75 (d, 1H, J = 8.3 Hz), 6.68 (d, 1H, J = 8.0 Hz), 6.66 (d, 1H, J = 2.0 Hz), 6.54 (dd, 1H, J = 2.0, 8.0 Hz), 6.32 (d, 1H, J = 15.8 Hz), 3.43 (t, 2H, J = 7.5 Hz), 2.68 (t, 2H, J = 7.5 Hz). 13C NMR (125 MHz, CD3OD) delta: 169.2, 148.7, 146.7, 146.2, 144.8, 142.1, 132.1, 128.3, 122.1, 121.0, 118.4, 116.9, 116.43, 116.38 115.0, 42.6, 36.0. FABMS calcd for C17H18NO5 (M+H): 316.1185. Found: 316.1178. All spectral data agreed with previously reported data [10].

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 138,p. 1066 - 1075

81
[ 331-39-5 ]
[ 657-27-2 ]
C₁₅H₂₀N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%		1) Weigh 90mg (0.5mmol) of caffeic acid into a 10mL round bottom flask.4 mL of DCM (dichloromethane) was added dropwise to the round bottom flask to dissolve the caffeic acid;2) 280 muL (about 2 mmol) of triethylamine was further added to the round bottom flask, and the mixture was cooled to 0 C with stirring in an ice water bath;3) Add to the round bottom flask in an ice water bath and stirringEDCI (1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride) 190 mg (1 mmol) and DMAP (4-dimethylaminopyridine) 122 mg (1 mmol), 30 min later Further, 91 mg (0.5 mmol) of L-lysine hydrochloride was added to the bottom flask, and the temperature was raised to room temperature (25 C), and the reaction was continued under stirring for 24 hours;4) After the end of the reaction, the solvent was evaporated under reduced pressure (rotary evaporation, -0.08 MPa, 45 C), and then added with 8 mL of ethyl acetate.After suction filtration, the organic phase of the upper layer of the filtrate was washed successively with a 5% aqueous solution of sodium hydrogencarbonate and saturated brine, dried over anhydrous sodium sulfate, and evaporated to dryness (evaporation, -0.08 MPa, 45 C) Crude yellow solid product, column chromatography (multiple of the total volume to the mass of the crude solid product: gradient I is 10 times, gradient II is 16 times, gradient III is 5 times) and then caffeic acid-lysine (80.2 mg) , yield 52%).

Reference： [1]Patent: CN106349099,2018,B .Location in patent: Paragraph 0046; 0047; 0048; 0049; 0050; 0051

82
[ 331-39-5 ]
[ 404-70-6 ]
(E)-3-(3,4-dihydroxyphenyl)-N-(3-fluorophenethyl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; for 24.17h;	General procedure: A mixture of the acid (1 mmol), amine (1 mmol), HOBtH2O (1mmol) in CH2Cl2 (5 mL) and drops of DMF, if necessary, tomake a clear solution, was cooled to 0oC. Then EDCHCl (1 mmol) wasadded and the reaction mixture was stired at 0oC for 10 min and atroom temperature for 24 h. EtOAc (50 mL) and HCl 0.5 N (5 mL) were added, theorganic phase was succesfuly washed with H2O, brine, dried over Na2SO4and concentrated under reduced pressure. The crude product was purifiedby column chromatography to give the pure amide.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 1085 - 1089

83
[ 331-39-5 ]
[ 17609-47-1 ]
(E)-N-(caffeic acid)-L-valine ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%		General procedure: Feruloyl amino acid ethyl esters a1-3, b1-3 were synthesized from ferulic acid and different amino acid ethyl esters using 1-(3-dimethylaminopropyl)- 3-ethylcarbodiimide-hydrochloride (EDC) /1-hydroxybenzotriene (HOBt) method with some modifications.28 Ferulic acid (1.07 g, 5.5 mmol) and HOBt (0.74 g, 5.5 mmol) and EDC (0.99 g, 5.5 mmol) were dissolved in (11 mL) N,N-dimethylformamide (DMF), the reaction mixture was cooled at 0 ? and reacted for 10 min. Then, N-methyl morpholine (0.76 mL) and hydrochloride of HCl?NH2-CH(R)-COOR (C-protected amino acid) (5.5 mmol) in 8.5 mL CH2Cl2 were added and well mixed. The reaction was carried out at 0 ? for 1 h, followed by stirring at room temperature for 20 h. When the reaction was completed, the reaction solution was poured into (100 mL) 5% NaHCO3 and extracted with ethyl acetate (2×75 mL). Then, the organic phase was washed with water (2×50 mL) and brine (2×50 mL) before dring with anhydrous Na2SO4 for 24 h. After recovering the solvent under reduced pressure, the residue was purified by silica gel column chromatography (Ethyl acetate/Petroleum ether (2:1)) to give a1-a3. The preparation of acetylferuloyl amino acid ethyl esters b1-b3 was the same as feruloyl amino acid esters? except for the use acetylferulic acid as reaction material instead of ferulic acid. EDC/HOBt coupling method for the synthesis of caffeoyl amino acid ethyl esters c1-c6 was applied.5

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27

84
[ 331-39-5 ]
[ 2743-40-0 ]
(E)-N-(caffeic acid)-L-leucine ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%		General procedure: Feruloyl amino acid ethyl esters a1-3, b1-3 were synthesized from ferulic acid and different amino acid ethyl esters using 1-(3-dimethylaminopropyl)- 3-ethylcarbodiimide-hydrochloride (EDC) /1-hydroxybenzotriene (HOBt) method with some modifications.28 Ferulic acid (1.07 g, 5.5 mmol) and HOBt (0.74 g, 5.5 mmol) and EDC (0.99 g, 5.5 mmol) were dissolved in (11 mL) N,N-dimethylformamide (DMF), the reaction mixture was cooled at 0 ? and reacted for 10 min. Then, N-methyl morpholine (0.76 mL) and hydrochloride of HCl?NH2-CH(R)-COOR (C-protected amino acid) (5.5 mmol) in 8.5 mL CH2Cl2 were added and well mixed. The reaction was carried out at 0 ? for 1 h, followed by stirring at room temperature for 20 h. When the reaction was completed, the reaction solution was poured into (100 mL) 5% NaHCO3 and extracted with ethyl acetate (2×75 mL). Then, the organic phase was washed with water (2×50 mL) and brine (2×50 mL) before dring with anhydrous Na2SO4 for 24 h. After recovering the solvent under reduced pressure, the residue was purified by silica gel column chromatography (Ethyl acetate/Petroleum ether (2:1)) to give a1-a3. The preparation of acetylferuloyl amino acid ethyl esters b1-b3 was the same as feruloyl amino acid esters? except for the use acetylferulic acid as reaction material instead of ferulic acid. EDC/HOBt coupling method for the synthesis of caffeoyl amino acid ethyl esters c1-c6 was applied.5

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27

85
[ 331-39-5 ]
[ 485-80-3 ]
[ 1135-24-6 ]
[ 2316-26-9 ]
[ 537-73-5 ]

Reference： [1]ChemCatChem,2019,vol. 11,p. 3227 - 3233

86
[ 331-39-5 ]
[ 1421-65-4 ]
[ 120094-83-9 ]

Yield	Reaction Conditions	Operation in experiment
60.16%	With triethanolamine; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; for 16.5h;	Place L-dopa methyl hydrochloride (9.99 mmol, 2.47 g) in a round bottom flask, add DMF (10 mL) to dissolve,Place in an ice bath (0-5 C) and stir for 10 minutes, and then add the prepared caffeic acid (8.33 mmol, 1.50 g) in dichloromethane (20 mL) dropwise.After the dropwise addition, PyBOP (8.33 mmol, 4.33 g) was added in portions, and triethanolamine (24.98 mmol, 3.33 mL) was added at the same time.After 30 minutes of reaction, stir at room temperature for 16 h.The reaction was monitored by TLC (developing solvent: n-hexane-ethyl acetate-methanol, 5: 4: 1), and the reaction was complete.The solvent was recovered under reduced pressure, and the mixture was allowed to cool and extracted with ethyl acetate (3 × 25 mL). The organic phases were combined, followed by 1 M hydrochloric acid solution,10% sodium bicarbonate solution, water, saturated sodium chloride (3 × 25 mL), dried over anhydrous sodium sulfate, spin-dried,Column chromatography (eluent: n-hexane: ethyl acetate: methanol = 60: 35: 5), dried under reduced pressure,A light yellow powder (I-1) (1.87 g) was obtained.The yield was 60.16%. Mp: 162.1-162.8

Reference： [1]Patent: CN110563602,2019,A .Location in patent: Paragraph 0012; 0013

87
[ 2740-83-2 ]
[ 331-39-5 ]
(E)-3-(3,4-dihydroxyphenyl)-N-(3-(trifluoromethyl)benzyl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.2%		Caffeic acid (200 mg, 1.11 mmol), HOBt (150 mg, 1.11 mmol) and EDCI (212 mg, 1.11 mmol) were dissolved in DMF (3 mL) and stirred at room temperature for 20 minutes. After 20 minutes, 3- (trifluoromethyl) benzylamine (0.16 mL, 1.11 mmol) was added thereto and stirred at room temperature for 20 minutes.After 20 minutes DIPEA (0.39 mL, 2.22 mmol) was added and stirred for 16 h and then extracted with EtOAc, water, 1N-HCl and brine.The organic layer was dried over anhydrous Mg 2 SO 4, concentrated under reduced pressure, and purified by column chromatography.Yield 80.2%;

Reference： [1]Patent: KR101693034,2017,B1 .Location in patent: Paragraph 0093; 0173-0176

88
[ 20283-92-5 ]
[ 331-39-5 ]
[ 23028-17-3 ]

Yield	Reaction Conditions	Operation in experiment
	In aq. buffer;pH 7.4;Electrochemical reaction;	20 mM ammonium formate buffer was prepared with water/acetonitrile(50/50, v/v) and used through out the electrochemical experiments.For the electrochemical conversion, a 100 muM sample of target compound in a 20 mM buffer solution was used. The pH was adjusted to 7.4 with 20-22% ammonium hydroxide solution. A setup for on-line oxidation of metabolites by EC is shown in Fig. S1(a) (see Supplementary material). The samples were injected into the electrochemical flow-through cell at a constant flow rate of 10 muL/min with asyringe pump (1 mL glass syringe). The potentiostat was set to performa potential scan from 0 to 3 V at a scan rate of 100 mV/s. Potential and applied by the electrochemical cell are shown in Table S1. After electrochemical conversion of target analytes, the products were flowed to MS for real-time monitoring.

Reference： [1]Food Chemistry,2020,vol. 315

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P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 331-39-5 ] {[proInfo.proName]}

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[ 331-39-5 ] Synthesis Path-Upstream 1~12

[ 331-39-5 ] Synthesis Path-Downstream 1~88

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