[ CAS No. 138505-25-6 ] {[proInfo.proName]}

Name: 138505-25-6|5-Bromo-2-isopropoxybenzaldehyde|97%
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Quality Control of [ 138505-25-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 138505-25-6 ]

CAS No. :	138505-25-6	MDL No. :	MFCD02257437
Formula :	C₁₀H₁₁BrO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GRLHVQABEZCTRD-UHFFFAOYSA-N
M.W :	243.10	Pubchem ID :	819973
Synonyms :

Calculated chemistry of [ 138505-25-6 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.3
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	55.64
TPSA :	26.3 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.35 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.52
Log Po/w (XLOGP3) :	3.43
Log Po/w (WLOGP) :	3.05
Log Po/w (MLOGP) :	2.44
Log Po/w (SILICOS-IT) :	3.18
Consensus Log Po/w :	2.92

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.65
Solubility :	0.0542 mg/ml ; 0.000223 mol/l
Class :	Soluble
Log S (Ali) :	-3.66
Solubility :	0.0528 mg/ml ; 0.000217 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.77
Solubility :	0.0415 mg/ml ; 0.000171 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.69

Safety of [ 138505-25-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 138505-25-6 ]

* 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 [ 138505-25-6 ]
Downstream synthetic route of [ 138505-25-6 ]

[ 138505-25-6 ] Synthesis Path-Upstream 1~3

1
[ 75-30-9 ]
[ 1761-61-1 ]
[ 138505-25-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate; caesium carbonate In <i>N</i>-methyl-acetamide	Step A: Synthesis of 5-bromo-2-isopropoxybenzaldehyde AX. To a suspension of potassium carbonate (34.4 g, 249 mmol) and cesium carbonate (16.2 g, 50 mmol) in dimethylformamide were added 5-bromosalicaldehyde (25.0 g, 124 mmol) and 2-iodopropane (25.0 mL, 249 mmol). The suspension was stirred at room temperature overnight, then at 70° C. for 4 hrs. The volatiles were removed, and the residue was partitioned between methyl t-butylether and water. The aqueous layer was extracted with methyl t-butylether and the combined organic phases were washed with water, sodium hydroxide, and brine, and then dried over magnesium sulfate. Concentration to dryness afforded compound AX (30.0 g) as a pale yellow oil in 99percent yield. ¹H NMR (CDCl₃, 400 MHz): δ 1.40 (d, J=6.3 Hz, 6H), 4.65 (sept., J=6.0 Hz, 1H), 6.89 (d, J=9.0 Hz, 1H), 7.59 (dd, J=9.0 and 2.7 Hz, 1H), 7.91 (d, J=2.7 Hz, 1H), 10.39 (s, 1H).
99%	With potassium carbonate; caesium carbonate In N,N-dimethyl-formamide at 20 - 70℃; for 4 h;	To a suspension of potassium carbonate (34.4 g, 249 mmol) and cesium carbonate (16.2 g, 50 mmol) in dimethylformamide were added 5-bromosalicaldehyde (25.0 g, 124 mmol) and 2-iodopropane (25.0 mL, 249 mmol). The suspension was stirred at room temperature overnight, then at 70° C. for 4 hrs. The volatiles were removed, and the residue was partitioned between methyl t-butylether and water. The aqueous layer was extracted with methyl t-butylether and the combined organic phases were washed with water, sodium hydroxide, and brine, and then dried over magnesium sulfate. Concentration to dryness afforded compound AX (30.0 g) as a pale yellow oil in 99percent yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.40 (d, J=6.3 Hz, 6H), 4.65 (sept., J=6.0 Hz, 1H), 6.89 (d, J=9.0 Hz, 1H), 7.59 (dd, J=9.0 and 2.7 Hz, 1H), 7.91 (d, J=2.7 Hz, 1H), 10.39 (s, 1H).
98%	With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 0.5 h; Inert atmosphere	To a solution of 5-bromo-2-hydroxybenzaldehyde 3 (600 mg, 3.0mmol) and 2-iodopropane (1.4 ml, 15 mmol) in dry-DMF wasadded K2CO3 (3.2 g, 24 mmol). The mixture was heated at 60 Cunder N2 in oil bath. The mixture was stirred for 30 min. The excessK2CO3 was quenched with 1 M aq. HCl. After the addition 1 M aq.HCl, extracted with ethyl acetate and washed with brine. Theorganic layer was dried over Na2SO4, filtered and concentrated. The residue waspurified by column chromatography on silica gel (hexane / AcOEt = 20 : 1 ) to give5-bromo-2-isopropoxybenzaldehyde (712.6 mg, 98percent) as a colorless oil. 1H NMR (270MHz, CDCl3) δ 1.40 (d. J = 5.94 Hz, 6H), 4.58-4.71 (m, 1H), 6.89 (d, J = 9.2 Hz, 1H),7.59 (d, J = 8.6 Hz, 1H), 7.91 (s, 1H), 10.40 (s, 1H).

Reference： [1] Patent: US2009/202480, 2009, A1,
[2] Tetrahedron Letters, 2010, vol. 51, # 4, p. 709 - 713
[3] Patent: US9115095, 2015, B2, . Location in patent: Page/Page column 44; 45
[4] Synlett, 2016, vol. 27, # 16, p. 2352 - 2356
[5] Helvetica Chimica Acta, 2005, vol. 88, # 5, p. 936 - 949
[6] Synthesis, 2005, # 19, p. 3362 - 3372
[7] Chemical Communications, 2009, # 40, p. 5990 - 5992
[8] Tetrahedron, 2003, vol. 59, # 25, p. 4525 - 4531
[9] Patent: US5750549, 1998, A,
[10] Organic Letters, 2009, vol. 11, # 14, p. 2972 - 2975
[11] Patent: US2011/9621, 2011, A1, . Location in patent: Page/Page column 6-7

2
[ 22921-58-0 ]
[ 138505-25-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃;	To a stirred solution of 2- isopropoxybenzaldehyde (0.51 g, 3.1 mmol), in DMF (10 ml) NBS (0.55 g, 3.1 mmol) was added and the reaction mixture was stirred overnight at room temperature. The reaction was quenched with NaHCO₃ solution and extracted in EtOAc (50 ml). The organic layer was washed with H₂O, dried over MgSO₄ and filtered. The filtrate was evaporated to dryness to give the title compound (0.62 g, 82percent) as light yellow oil. ¹ H-NMR (CDCI₃) 10.37 (s, 1 H); 7.89 (d, 1 H, J = 2.52 Hz); 7.55 (dd, 1 H, J = 8.85, 2.58 Hz); 6.87 (d, 1 H, J = 8.88 Hz); 4.67 - 4.58 (m, 1 H); 1.35 (d, 6H, J = 6.03 Hz).

Reference： [1] Patent: WO2010/43000, 2010, A1, . Location in patent: Page/Page column 78-79

3
[ 75-26-3 ]
[ 1761-61-1 ]
[ 138505-25-6 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1991, p. 2783 - 2787
[2] European Journal of Organic Chemistry, 2018, vol. 2018, # 33, p. 4614 - 4627

[ 138505-25-6 ] Synthesis Path-Downstream 1~43

1
[ 138505-25-6 ]
[ 138505-26-7 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 2783 - 2787

2
[ 75-26-3 ]
[ 1761-61-1 ]
[ 138505-25-6 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 2783 - 2787
[2]European Journal of Organic Chemistry,2018,vol. 2018,p. 4614 - 4627

3
[ 138505-25-6 ]
[ 19493-09-5 ]
[ 16602-27-0 ]

Reference： [1]Helvetica Chimica Acta,2005,vol. 88,p. 936 - 949
[2]Tetrahedron,2003,vol. 59,p. 4525 - 4531

4
[ 75-30-9 ]
[ 1761-61-1 ]
[ 138505-25-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate; caesium carbonate; In N-methyl-acetamide;	Step A: Synthesis of 5-bromo-2-isopropoxybenzaldehyde AX. To a suspension of potassium carbonate (34.4 g, 249 mmol) and cesium carbonate (16.2 g, 50 mmol) in dimethylformamide were added 5-bromosalicaldehyde (25.0 g, 124 mmol) and 2-iodopropane (25.0 mL, 249 mmol). The suspension was stirred at room temperature overnight, then at 70 C. for 4 hrs. The volatiles were removed, and the residue was partitioned between methyl t-butylether and water. The aqueous layer was extracted with methyl t-butylether and the combined organic phases were washed with water, sodium hydroxide, and brine, and then dried over magnesium sulfate. Concentration to dryness afforded compound AX (30.0 g) as a pale yellow oil in 99% yield. 1H NMR (CDCl3, 400 MHz): delta 1.40 (d, J=6.3 Hz, 6H), 4.65 (sept., J=6.0 Hz, 1H), 6.89 (d, J=9.0 Hz, 1H), 7.59 (dd, J=9.0 and 2.7 Hz, 1H), 7.91 (d, J=2.7 Hz, 1H), 10.39 (s, 1H).
99%	With potassium carbonate; caesium carbonate; In N,N-dimethyl-formamide; at 20 - 70℃; for 4h;	To a suspension of potassium carbonate (34.4 g, 249 mmol) and cesium carbonate (16.2 g, 50 mmol) in dimethylformamide were added 5-bromosalicaldehyde (25.0 g, 124 mmol) and 2-iodopropane (25.0 mL, 249 mmol). The suspension was stirred at room temperature overnight, then at 70 C. for 4 hrs. The volatiles were removed, and the residue was partitioned between methyl t-butylether and water. The aqueous layer was extracted with methyl t-butylether and the combined organic phases were washed with water, sodium hydroxide, and brine, and then dried over magnesium sulfate. Concentration to dryness afforded compound AX (30.0 g) as a pale yellow oil in 99% yield. 1H NMR (CDCl3, 400 MHz): delta (ppm) 1.40 (d, J=6.3 Hz, 6H), 4.65 (sept., J=6.0 Hz, 1H), 6.89 (d, J=9.0 Hz, 1H), 7.59 (dd, J=9.0 and 2.7 Hz, 1H), 7.91 (d, J=2.7 Hz, 1H), 10.39 (s, 1H).
98%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 0.5h;Inert atmosphere;	To a solution of 5-bromo-2-hydroxybenzaldehyde 3 (600 mg, 3.0mmol) and 2-iodopropane (1.4 ml, 15 mmol) in dry-DMF wasadded K2CO3 (3.2 g, 24 mmol). The mixture was heated at 60 Cunder N2 in oil bath. The mixture was stirred for 30 min. The excessK2CO3 was quenched with 1 M aq. HCl. After the addition 1 M aq.HCl, extracted with ethyl acetate and washed with brine. Theorganic layer was dried over Na2SO4, filtered and concentrated. The residue waspurified by column chromatography on silica gel (hexane / AcOEt = 20 : 1 ) to give5-bromo-2-isopropoxybenzaldehyde (712.6 mg, 98%) as a colorless oil. 1H NMR (270MHz, CDCl3) delta 1.40 (d. J = 5.94 Hz, 6H), 4.58-4.71 (m, 1H), 6.89 (d, J = 9.2 Hz, 1H),7.59 (d, J = 8.6 Hz, 1H), 7.91 (s, 1H), 10.40 (s, 1H).

	With potassium carbonate; In N,N-dimethyl-formamide;	Step A 5-Bromo-2-isopropoxy-benzaldehyde To a solution of 5-bromosalicylaldehyde (5.0 gm, 0.025 mol) in DMF (40 mL) were added powdered potassium carbonate (5.15 gm, 0.037 mol) and 2-iodopropane (3.5 mL, 0.035 mol) dropwise with stirring. The mixture was stirred overnight at room temperature, partitioned between diethyl ether and water. The aqueous was extracted with ether, and the combined organic layers were washed with water, saturated brine solution, dried (Na2 SO4), and evaporated to afford 6.0 gm of pure title compound.
	With potassium carbonate; caesium carbonate; In N,N-dimethyl-formamide;	1: Preparation of trans-3-(4-isopropoxy-3-vinylphenyl)acrylic acidtrans-3-(4-Isopropoxy-3-vinylphenyl)acrylic acid was prepared by reacting 5-bromo-2-hydroxybenzaldehyde with 2-iodopropane in DMF in the presence of K2CO3 and Cs2CO3 to form 5-bromo-2-isopropoxybenzaldehyde, then reacting this with ethyl acrylate in anhydrous DMF (dimethylformamide) in the presence of Pd(OAc)2 and P(o-Tol)3 and also triethylamine to form trans-3-(3-formyl-4-isopropoxyphenyl)ethyl acrylate, reacting this with methyltriphenylphosphonium bromide and BuLi in anhydrous THF (tetrahydrofuran) to form trans-3-(4-isopropoxy-3-vinylphenyl)ethyl acrylate and finally reacting this in 1,4-dioxane with an aqueous KOH solution to form trans-3-(4-isopropoxy-3-vinylphenyl)acrylic acid. This reaction sequence is described in more detail in F. Koc, F. Michalek, L. Rumi, W. Bannwarth, R. Haag, Synthesis 2005, 3362-3372.

Reference： [1]Patent: US2009/202480,2009,A1
[2]Tetrahedron Letters,2010,vol. 51,p. 709 - 713
[3]Patent: US9115095,2015,B2 .Location in patent: Page/Page column 44; 45
[4]Synlett,2016,vol. 27,p. 2352 - 2356
[5]Helvetica Chimica Acta,2005,vol. 88,p. 936 - 949
[6]Chemical Communications,2009,p. 5990 - 5992
[7]Tetrahedron,2003,vol. 59,p. 4525 - 4531
[8]Patent: US5750549,1998,A
[9]Organic Letters,2009,vol. 11,p. 2972 - 2975
[10]Patent: US2011/9621,2011,A1 .Location in patent: Page/Page column 6-7

5
[ 138505-25-6 ]
[ 140-88-5 ]
[ 876013-89-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;palladium diacetate; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide;	1: Preparation of trans-3-(4-isopropoxy-3-vinylphenyl)acrylic acidtrans-3-(4-Isopropoxy-3-vinylphenyl)acrylic acid was prepared by reacting 5-bromo-2-hydroxybenzaldehyde with 2-iodopropane in DMF in the presence of K2CO3 and Cs2CO3 to form <strong>[138505-25-6]5-bromo-2-isopropoxybenzaldehyde</strong>, then reacting this with ethyl acrylate in anhydrous DMF (dimethylformamide) in the presence of Pd(OAc)2 and P(o-Tol)3 and also triethylamine to form trans-3-(3-formyl-4-isopropoxyphenyl)ethyl acrylate, reacting this with methyltriphenylphosphonium bromide and BuLi in anhydrous THF (tetrahydrofuran) to form trans-3-(4-isopropoxy-3-vinylphenyl)ethyl acrylate and finally reacting this in 1,4-dioxane with an aqueous KOH solution to form trans-3-(4-isopropoxy-3-vinylphenyl)acrylic acid. This reaction sequence is described in more detail in F. Koc, F. Michalek, L. Rumi, W. Bannwarth, R. Haag, Synthesis 2005, 3362-3372.

Reference： [1]Synthesis,2005,p. 3362 - 3372
[2]Patent: US2011/9621,2011,A1 .Location in patent: Page/Page column 1

6
[ 138505-25-6 ]
[ 876013-91-1 ]

Reference： [1]Synthesis,2005,p. 3362 - 3372

7
[ 138505-25-6 ]
[ 876013-90-0 ]

Reference： [1]Synthesis,2005,p. 3362 - 3372

8
[ 138505-25-6 ]
[ 133593-76-7 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 2783 - 2787

9
[ 138505-25-6 ]
[ 133593-77-8 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 2783 - 2787

10
[ 138505-25-6 ]
[ 133773-24-7 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 2783 - 2787

11
[ 138505-25-6 ]
[ 133593-79-0 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 2783 - 2787

12
[ 138505-25-6 ]
[ 133593-78-9 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 2783 - 2787

13
[ 138505-25-6 ]
[ 138505-27-8 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 2783 - 2787

14
[ 138505-25-6 ]
5-(4-Hydroxy-3-methoxy-phenyl)-7-(4-hydroxy-3-methyl-benzyl)-6-methyl-naphthalene-1,3-diol [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 2783 - 2787

15
[ 138505-25-6 ]
[ 138505-24-5 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 2783 - 2787

Yield	Reaction Conditions	Operation in experiment
		(1) 10 g of 4-bromosalicyl aldehyde and 10 ml of propyl 2-iodide were treated in the same manner as in Example 114(1) to give 6.5 g of 2-(2-propoxy)-5-bromobenzaldehyde. Oily product

17
[ 138505-25-6 ]
[ 190270-92-9 ]

Yield	Reaction Conditions	Operation in experiment
	In hexane; water; ethyl acetate; N,N-dimethyl-formamide;	Step A 5-Cyano-2-isopropoxy-benzaldehyde The title compound was prepared by the treatment of <strong>[138505-25-6]5-bromo-2-isopropoxy-benzaldehyde</strong> (3.5 gm, 0.014 mol) with copper(I) cyanide (2.5 gm, 0.028 mol) in refluxing DMF for 28 hours. The cooled mixture was poured into a mixture of water (100 mL) and ethyl acetate (100 mL). The mixture was filtered through a pad of Celite, the organic layer separated, washed with saturated brine solution, dried (Na2SO4), and evaporated. The title compound was purified by flash chromatography eluding with 15% ethyl acetate in hexane; yield 1.9 gm of a white solid.

Reference： [1]Patent: US5750549,1998,A

18
[ 1765-93-1 ]
[ 497-19-8 ]
[ 138505-25-6 ]
2-isopropoxy-5-(4-fluorophenyl)-benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	tetrakis(triphenylphosphine)palladium (0); In 1,2-dimethoxyethane; hexane;	Step A 2-Isopropoxy-5-(4-fluorophenyl)-benzaldehyde To a solution of <strong>[138505-25-6]5-bromo-2-isopropoxy-benzaldehyde</strong> (504 mg, 2.07 mmol) in 1,2-dimethoxyethane (5 mL) were added tetrakis(triphenylphosphine)palladium(0) (87 mg, 0.075 mmol), 2M aqueous sodium carbonate (2.5 mL), and 4-fluorobenzeneboronic acid (396 mg, 2.83 mmol). The reaction mixture was stirred for 2 hours at reflux temperature, cooled, diluted with ethyl acetate, washed with water, saturated brine solution, dried (Na2 SO4), and evaporated. The title compound was purified by flash chromatography eluding with 4% diethyl ether in hexane; yield 347 mg.

Reference： [1]Patent: US5750549,1998,A

19
[ 1779-49-3 ]
[ 138505-25-6 ]
[ 16602-27-0 ]

Yield	Reaction Conditions	Operation in experiment
95%	With n-butyllithium; ammonium chloride; In tetrahydrofuran;	Step B: Synthesis of 4-bromo-1-isopropoxy-2-vinylbenzene AY. To a suspension of methyltriphenylphosphonium bromide (41.1 g, 115 mmol) in THF (1.2 L) cooled to -70 C., was added n-butyllithium (123 mmol, 2.5 M in hexanes). The mixture was stirred for a further 10 min, and then allowed to warm up to 0 C. and stir at this temperature for 10 min. The reaction mixture is then cooled again at -50 C., and <strong>[138505-25-6]5-bromo-2-isopropoxybenzaldehyde</strong> (20.0 g, 82.2 mmol) in solution in THF (5 mL) was added. The mixture was stirred for 10 min, then allowed to warm up to room temperature. An ammonium chloride solution was added and the reaction mixture was diluted with a mixture methyl t-butylether/hexane, filtered through celite, and then dried over magnesium sulfate. The solvent was removed in vacuo to afford compound AY (18.9 g) as a pale yellow oil in 95% yield. 1H NMR (CDCl3, 400 MHz): delta 1.34 (d, J=6.0 Hz, 6H), 4.50 (sept., J=6.0 Hz, 1H), 5.27 (dd, J=11.0 and 1.1 Hz, 1H), 5.71 (dd, J=17.9 and 1.2 Hz, 1H), 6.75 (d, J=8.7 Hz, 1H), 6.97 (dd, J=17.7 and 11.2 Hz, 1H), 7.28 (dd, J=8.7 and 2.5 Hz, 1H), 7.57 (d, J=2.5 Hz, 1H).
95%		To a suspension of methyltriphenylphosphonium bromide (41.1 g, 115 mmol) in anhydrous THF (1.2 L) was added n-butyllithium (123 mmol, 2.5 M in hexanes) at -70 C. The mixture was stirred for a further 10 min, and then allowed to warm up to 0 C. and stirred at this temperature for 10 min. The reaction mixture is then cooled again at -50 C., and <strong>[138505-25-6]5-bromo-2-isopropoxybenzaldehyde</strong> (20.0 g, 82.2 mmol) in solution in anhydrous THF (5 mL) was added. The mixture was stirred for 10 min, and then allowed to warm up to room temperature. An ammonium chloride solution was added and the reaction mixture was diluted with a mixture methyl t-butylether/hexane, filtered through celite, and then dried over magnesium sulfate. The solvent was removed in vacuo to afford compound AY (18.9 g) as a pale yellow oil in 95% yield. 1H NMR (CDCl3, 400 MHz): delta (ppm) 1.34 (d, J=6.0 Hz, 6H), 4.50 (sept., J=6.0 Hz, 1H), 5.27 (dd, J=11.0 and 1.1 Hz, 1H), 5.71 (dd, J=17.9 and 1.2 Hz, 1H), 6.75 (d, J=8.7 Hz, 1H), 6.97 (dd, J=17.7 and 11.2 Hz, 1H), 7.28 (dd, J=8.7 and 2.5 Hz, 1H), 7.57 (d, J=2.5 Hz, 1H).

Reference： [1]Patent: US2009/202480,2009,A1
[2]Patent: US9115095,2015,B2 .Location in patent: Page/Page column 44; 45; 46
[3]Chemical Communications,2009,p. 5990 - 5992
[4]European Journal of Organic Chemistry,2018,vol. 2018,p. 4614 - 4627
[5]Journal of the American Chemical Society,2018,vol. 140,p. 13151 - 13155

20
[ 138505-25-6 ]
[ 108-59-8 ]
[ 1173178-94-3 ]

Reference： [1]Organic Letters,2009,vol. 11,p. 2972 - 2975

21
[ 288-32-4 ]
[ 138505-25-6 ]
[ 1210502-10-5 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 709 - 713

22
[ 1692-15-5 ]
[ 138505-25-6 ]
[ 1210502-11-6 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 709 - 713

23
[ 4890-63-5 ]
[ 138505-25-6 ]
[ 1296134-48-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a stirred solution of phenyl-acetylene (0.27 ml, 2.46 mmol) in anhydrous THF (3 ml) 2M iPrMgCI in THF (1.25 ml) was added drop wise at 0 5C under N2. After stirring for 15 min, the solution of product of Step A (0.5 g, 2.06 mmol) in anhydrous THF (2 ml) was added drop wise and the mixture was stirred for 1 h at room temperature. The mixture was quenched with saturated NH4CI and extracted with EtOAc (50 ml). The organic layer was washed with H2O, dried over MgSO4. and filtered. The filtrate was evaporated to dryness to give a creamy paste (0.59 g; 83%). [1H-NMR (CDCI3) 7.68 (d, 1 H, J = 2.49 Hz); 7.46 - 7.43 (m, 2H); 7.36 (dd, 1 H, J = 8.75, 2.54 Hz); 7.32-7.28 (m, 3H); 6.79 (d, 1 H, J = 6.77 Hz); 5.79 (d, 1 H, J = 5.23 Hz); 4.64 - 4.58 (m, 1 H); 3.13 (d, 1 H, J = 5.91 Hz); 1 .37 (d, 6H)]. This was dissolved in dioxane (10 ml) and MnO2 (1 g) was added to it. The resulting suspension was stirred for 6 h at reflux, then filtered through Celite and the solvent was evaporated to dryness to give the title compound (0.54 g, 76.5%), as light yellow paste. 1H-NMR (CDCI3) 8.00 (d, 1 H, J = 2.61 Hz); 7.61 - 7.52 (m, 3H); 7.44 - 7.35 (m, 3H); 6.88 (d, 1 H, J = 8.91 Hz); 4.68 - 4.60 (m, 1 H); 1 .36 (d, 6H).

Reference： [1]Patent: WO2010/43000,2010,A1 .Location in patent: Page/Page column 79

24
[ 22921-58-0 ]
[ 138505-25-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃;	To a stirred solution of 2- isopropoxybenzaldehyde (0.51 g, 3.1 mmol), in DMF (10 ml) NBS (0.55 g, 3.1 mmol) was added and the reaction mixture was stirred overnight at room temperature. The reaction was quenched with NaHCO3 solution and extracted in EtOAc (50 ml). The organic layer was washed with H2O, dried over MgSO4 and filtered. The filtrate was evaporated to dryness to give the title compound (0.62 g, 82%) as light yellow oil. 1 H-NMR (CDCI3) 10.37 (s, 1 H); 7.89 (d, 1 H, J = 2.52 Hz); 7.55 (dd, 1 H, J = 8.85, 2.58 Hz); 6.87 (d, 1 H, J = 8.88 Hz); 4.67 - 4.58 (m, 1 H); 1.35 (d, 6H, J = 6.03 Hz).

Reference： [1]Patent: WO2010/43000,2010,A1 .Location in patent: Page/Page column 78-79

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ethyl[4-(trifluoromethyl)phenyl]-{4-(isopropoxy)-3-vinylphenyl}phosphinate [ No CAS ]