[ CAS No. 32454-35-6 ] {[proInfo.proName]}

Name: 32454-35-6|2-(4-Bromophenyl)-2-methylpropanoic acid|98%
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Quality Control of [ 32454-35-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 32454-35-6 ]

CAS No. :	32454-35-6	MDL No. :	MFCD02684220
Formula :	C₁₀H₁₁BrO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	AKVOQXBQLXOEEF-UHFFFAOYSA-N
M.W :	243.10	Pubchem ID :	10933679
Synonyms :

Calculated chemistry of [ 32454-35-6 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.3
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	55.18
TPSA :	37.3 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.65 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.92
Log Po/w (XLOGP3) :	3.01
Log Po/w (WLOGP) :	2.81
Log Po/w (MLOGP) :	2.99
Log Po/w (SILICOS-IT) :	2.59
Consensus Log Po/w :	2.66

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.45
Solubility :	0.0857 mg/ml ; 0.000352 mol/l
Class :	Soluble
Log S (Ali) :	-3.46
Solubility :	0.0847 mg/ml ; 0.000348 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.45
Solubility :	0.0859 mg/ml ; 0.000353 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.46

Safety of [ 32454-35-6 ]

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 [ 32454-35-6 ]

* 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 [ 32454-35-6 ]
Downstream synthetic route of [ 32454-35-6 ]

[ 32454-35-6 ] Synthesis Path-Upstream 1~3

1
[ 67-56-1 ]
[ 32454-35-6 ]
[ 154825-97-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	at 80 - 85℃; for 16 - 18 h;	General procedure: To a well-stirred mixture of acid (80 mmol), alcohol (90 mmol), acetonitrile (162 mmol) and sulfuric acid (98percent, 94 mmol, 5 mL) was added at room temperature. Slowly heated to 80-85 °C and maintained between 80-85°C for16–18 h. The reaction mixture was cooled and added to 20percent sodium carbonate solution (100mL). The reaction mass was extracted in CH2Cl2 (50 mL × 2). The combined organic layer was washed with water (100 mL), dried over sodium sufate, and concentrated under reduced pressure to obtain corresponding ester (97–99percent) as the only product. Most example gave NMR pure product. Where minor impurities are formed, the product was purified over silica gel using ethyl acetate: petroleum ether (1:9).
79%	With sulfuric acid In toluene at 63 - 67℃; for 16 h; Industry scale	Step-3: Preparation of methyl 2-(4-bromophenyl)-2-methylpropionate For operational convenience the product from two or three batches of Step-2 are combined and used in this step. The wet material (on dry basis) from step-2 (575 Kg, purity of about 98.2percent) was charged into a reactor containing 1150 L of toluene. The mass was maintained for about 15 minutes or until a clear solution was obtained. The toluene layer was washed with sodium chloride solution (20percent in water) and separated. To the toluene layer, methanol (300 L) was charged followed by sulphuric acid addition at 25-35° C. The reaction mass temperature was gradually raised to 63-67° C. and stirred for 16 hours or until complete consumption of 2-(4-bromophenyl)-2-methylpropanoic acid as indicated by GC analysis. The mass was gradually cooled to 25-35° C. and then washed with water (3500 L), sodium carbonate solution (2percent in water) and sodium chloride (10percent solution in water) successively. Organic phase was subjected to distillation under reduced pressure to obtain methyl 2-(4-bromophenyl)-2-methylpropionate (480 Kg, 79percent yield, GC purity: 99.2percent).
79%	With sulfuric acid In toluene at 63 - 67℃; for 16 h; Industry scale	Step-3: Preparation of methyl 2-(4-bromophenyl)-2-methylpropionate: For operational convenience the product from two or three batches of Step-2 are combined and used in this step. The wet material (on dry basis) from step-2 (575 Kg, purity of about 98.2percent) was charged into a reactor containing 1150 L of toluene. The mass was maintained for about 15 minutes or until a clear solution was obtained. The toluene layer was washed with sodium chloride solution (20percent in water) and separated. To the toluene layer, methanol (300 L) was charged followed by sulphuric acid addition at 25-35°C. The reaction mass temperature was gradually raised to 63-67°C and stirred for 16 hours or until complete consumption of 2-(4-bromophenyl)-2-methylpropanoic acid as indicated by GC analysis. The mass was gradually cooled to 25-35°C and then washed with water (3500 L), sodium carbonate solution (2percent in water) and sodium chloride (10percent solution in water) successively. The organic phase was subjected to distillation under reduced pressure to obtain methyl 2-(4-bromophenyl)-2-methylpropionate (480 Kg, 79percent yield, GC purity: 99.2percent).

Reference： [1] Synthetic Communications, 2014, vol. 44, # 6, p. 836 - 846
[2] Patent: US2012/309973, 2012, A1, . Location in patent: Page/Page column 4
[3] Patent: EP2532644, 2012, A1, . Location in patent: Page/Page column 6

2
[ 1634-04-4 ]
[ 32454-35-6 ]
[ 154825-97-5 ]

Yield	Reaction Conditions	Operation in experiment
93%	Reflux	General procedure: To a well-stirred mixture of acid (80 mmol) in TBME (50 mL) was added sulfuric acid (1.8 g, 1 mL) at room temperature and refluxed for 16-18 h. The reaction mixture was cooled and added to 20percent sodium carbonate solution (100 mL). The reaction mass was extracted in dichloromethane (50 mL .x. 2). The combined organic layer was washed with water (100 mL), dried over sodium sulfate, and concentrated under reduced pressure to obtain methyl ester (73-97percent) as the only product. Most examples gave NMR pure product. Where minor impurities were formed, the product was purified over silica gel using ethyl acetate: petroleum ether (1:9).

Reference： [1] Tetrahedron Letters, 2011, vol. 52, # 33, p. 4262 - 4265

3
[ 32454-35-6 ]
[ 214973-83-8 ]

Reference： [1] Patent: US2017/137385, 2017, A1,

[ 32454-35-6 ] Synthesis Path-Downstream 1~87

1
[ 826-55-1 ]
[ 32454-35-6 ]

Yield	Reaction Conditions	Operation in experiment
81%		Example 3:; 2-Methyl-2-phenylpropanoic acid (5 g, 0.0304 moles) and water (50 ml) were added to three-necked round bottomed flask at ambient temperature (25 C to 30 C). To the resulting mixture, sodium carbonate solution (20% in water) was added dropwise until the pH was about 7. To the resulting solution 8.7 g of bromine was added dropwise while maintaining the pH of reaction solution at about 7 by addition of sodium carbonate solution. The reaction mixture was stirred until complete consumption of 2-methyl-2-phenylpropanoic acid as determined by gas chromatographic analysis. The neutral reaction solution was acidified with 5N hydrochloric acid to pH 1 to 2. The aqueous solution was extracted with dichloromethane (3x50 ml). All organic layers were combined, dried with anhydrous sodium sulphate and evaporated to dryness. The resulting solid product was suspended in hexanes (50 ml) and filtered to recover the product, 6.0 g, 81% yield, GC purity 98.5% of 2-(4-bromophenyl)-2-methylpropanoic acid and 1.25% of 2-(3-bromophenyl)-2-methylpropanoic acid.
46.6%		Step-2: Preparation of 2-(4-bromophenyl)-2-methylpropanoic acidThe wet material (on dry basis) from step-1 (275 Kg, assay 98%) was charged into a reactor containing 6875 L of water and 660 Kg of sodium bicarbonate. Bromine (330 Kg) was fed slowly into the reactor during 3 hours at 25-35 C. and maintained for 10 hours at 25-35 C. Toluene (275 L) was charged into reactor and stirred for 15 minutes. The aqueous phase was discharged into another reactor and pH adjusted to about 5 with dilute hydrochloric acid (880 L of water and 440 L of hydrochloric acid) at 0-10 C. The resultant material was filtered and washed with water. The obtained wet product was treated with heptanes (700 L) to recover 190 Kg (46.6% yield) of 2-(4-bromophenyl)-2-methylpropanoic acid, GC purity: 99.28% of 2-(4-bromophenyl)-2-methylpropanoic acid and 0.72% of 2-(3-bromophenyl)-2-methylpropanoic acid,

Reference： [1]Patent: EP2532644,2012,A1 .Location in patent: Page/Page column 5
[2]Patent: US2012/309973,2012,A1 .Location in patent: Page/Page column 3-4
[3]Journal of the American Chemical Society,1957,vol. 79,p. 3432,3437

2
[ 32454-35-6 ]
[ 32454-37-8 ]

Yield	Reaction Conditions	Operation in experiment
100%		<strong>[32454-35-6]2-(4-Bromophenyl)-2-methylpropanoic acid</strong> (1 g, 4 mmol) in tetrahydrofuran (15.5 ml)was cooled to 0 C. 1M Borane in tetrahydrofuran (4.11 ml, 4.11 mmol) was slowly added to the reaction mixture. Once addition was complete, the reaction was warmed up to room temperature and stirred for 18 hours. Aqueous solution of 1N hydrochloric acid and water were added and reation solution extracted with ethyl acetate. Organic washed with brine, dried over sodium sulfate, filtered and concentrated to give 2-(4-bromophenyl)-2-methylpropan-1-ol (0.9 g, 100%) as a clear oil.

Reference： [1]Patent: US2010/197591,2010,A1 .Location in patent: Page/Page column 20
[2]Journal of the American Chemical Society,1957,vol. 79,p. 3432,3437
[3]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4150 - 4154
[4]Organic Letters,2017,vol. 19,p. 2626 - 2629

3
[ 14062-25-0 ]
[ 74-88-4 ]
[ 32454-35-6 ]

Reference： [1]Helvetica Chimica Acta,1971,vol. 54,p. 868 - 897

4
[ 101184-73-0 ]
[ 32454-35-6 ]

Yield	Reaction Conditions	Operation in experiment
5.3 g	With water; potassium hydroxide; In ethanol; for 20h;Reflux;	A solution of the intermediate obtained above (5 g, 22 mmoles) and of KOH (2.4 g) in a mixture of ethanol (25 mL) and water (7.5 mL) is heated at reflux for 20 hours. The reaction mixture is concentrated in vacuo, and the residue is taken up with ethyl ether (100 mL) and water (60 mL). The aqueous phase (free of organic solvent) is cooled to 10 C. and then acidified with a 37% HCl solution. The precipitate that forms is collected on a frit and dried in vacuo. Intermediate 599 (5.3 g) is obtained in the form of a white solid. 1H NMR (400 MHz, CDCl3): delta 9.00-8.00 (1H), 7.75 (d, 2H), 7.25 (d, 2H), 1.60 (s, 6H) IR (cm-1): 3347-2235, 1697

Reference： [1]Synthetic Communications,1996,vol. 26,p. 4699 - 4710
[2]Patent: US2017/137385,2017,A1 .Location in patent: Paragraph 0230; 0234; 0235; 0236
[3]Tetrahedron Letters,2020,vol. 61

5
[ 32454-35-6 ]
[ 75492-21-6 ]

Reference： [1]Journal of the American Chemical Society,1957,vol. 79,p. 3432,3437

6
[ 847358-99-0 ]
[ 32454-35-6 ]
4'-[(1S)-1-[[(1S)-1-[[(1-cyanocyclopropyl)amino]carbonyl]-3-fluoro-3-methylbutyl]amino]-2,2,2-trifluoroethyl]-α,α-dimethyl-[1,1'-biphenyl]-4-acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In DMF (N,N-dimethyl-formamide); water; at 80℃; for 3h;	Step 2: 4'-[(1S)-1-[[(1S)-1-[[(1-cyanocyclopropyl)amino]carbonyl]-3-fluoro-3- METHYLBUTVLLAMINOL-2, 2, 2-TRIFLUOROETHYLL-A, A-DIMETHYL-RL, L -BIPHENYLL-4-ACETIC acid; A stream of nitrogen was passed through a solution of DMF (4 mL) of the boronate from Example 3, Step 3 (160 mg), 2- (4-BROMOPHENYL)-2-METHYLPROPANOIC acid from Step 1 (77 mg) and 2 M NA2C03 (400 TIL) for 15 minutes followed by the addition of [1, l'-bis (diphenylphosphino) - ferrocene] dichloropalladium (II), complex (1 : 1) with dichloromethane (13 mg). The mixture was warmed to 80 C for 3 hours under nitrogen. The mixture was cooled to room temperature, poured into ice (10 g) and 1.0 N HC1 (15 mL) and extracted with 50 % ethyl acetate in diethyl ether (3 x 30 mL). The combined extracts were washed with brine and dried with magnesium sulfate. Removal of the solvent left a residue that was purified by chromatography on SI02 using ethyl acetate, hexanes and acetic acid (1: 3: 1% to 1: 1: 1 %) as eluants, followed by a swish using diethyl ether to yield the title compound. H NMR (CD3COCD3) 8 10.80 (1H, bs), 8.17 (1H, bs), 7.73 (2H, d), 7.69 (2H, d), 7.57 (2H, d), 7.55 (2H, d), 4. 36-4. 43 (1H, M), 3.54-3. 60 (1H, M), 1.93-2. 05 (2H, M), 1.63 (6H, s), 1.42-1. 50 (6H, M), 1.30-1. 40 (2H, M), 1. 06-1. 1 L (LH, M), 0.90-0. 97 (1H, M) ; leucine NH not observed. MS (+APCI) : 534.2 (M+1) +.

Reference： [1]Patent: WO2005/19161,2005,A1 .Location in patent: Page/Page column 66

7
[ 154825-97-5 ]
[ 32454-35-6 ]

Yield	Reaction Conditions	Operation in experiment
94%		Methyl 2-(4-bromophenyl)-2-methylpropanoate (24 g, 93.3 mmol), 2 M aqueous lithium hydroxide (200 mL) and 1,4-dioxane (250 mL) were heated to 50 C. for 5.5 hours. The reaction mixture was cooled to room temperature, made acidic with 2 M (aqueous hydrochloric acid and diluted with brine. The reaction mixture was extracted with ethyl acetate, dried over magnesium sulfate and concentrated to give 2-(4-bromophenyl)-2-methylpropanoic acid (21.4 g, 94%). 1H NMR (300 MHz, CDCl3): delta ppm 7.46 (dd, 2H), 7.27 (dd, 2H), 1.55 (s, 6H) ppm.
		EXAMPLE 12; 4 -R (1S)-1-[[(1S)-1-[[(1-cyanocyclopropyl)amino]carbonyl]-3-fluoro-3-methylbutyl]amino]-2,2,2- TRIFLUOROETHYLL-A, CT-DIMETHYL- (1, 1 -BI HENVLL-4-ACETIC acid; STEP 1 : 2- (4-BROMOPHENYL)-2-METHYLPROPANOIC acid; To a 0 C solution of diisopropylamine (1.52 mL) in THF (50 mL) was slowly added butyllithium (4.3 mL). The reaction mixture was stirred at 0 C for 15 minutes. It was cooled to-78 C and a solution of methyl 2- (4-bromophenyl) propanoate from Example 11 Step 2 (2.4 g) in THF (25 ML) was slowly added. The mixture was stirred at-78 C for 30 minutes. Then a solution of iodomethane (2.5 mL) in THF (25 mL) was added dropwise and the mixture was stirred at-78 C for 30 minutes then warmed up slowly to room temperature and stirred for 1 HOUR. H NMR showed 50% conversion. The reaction mixture was cooled to 0 C and 20 mL of potassium t-butoxid (1.0 M in THF) was added dropwise. The mixture was stirred at 0 C for 30 minutes, warmed up to room temperature and stirred for 1 hour. The reaction mixture was poured into ice (50 g) and saturated aqueous ammonium chloride (100 mL), extracted with ethyl acetate (3 x 100 mL). The combined extracts were washed with brine, dried with magnesium sulfate and the solvent removed in vacuo to yield a residue which was diluted with THF (30 ML) and methyl alcohol (15 mL). The solution was cooled to 0 C and 20 mL of lithium hydroxide (1.0 N) was added. The mixture was stirred at room temperature for 3 hours. Then the reaction mixture was poured into ice and 1N HC1 and extracted with dichloromethane (2 x 100 mL). The combined extracts were washed with brine, dried with magnesium sulfate and the solvent removed in vacuo. The residue was purified by swish using diethyl ether and hexanes to yield the title compound. 'H NMR (CD3COCD3) 8 10.85 (1H, bs), 7.53 (2H, d), 7.48 (2H, d), 1.50 (6H, s).
		Step A: Preparation of 2-(4-Bromophenyl)-2-methylpropanoic acid; [0525] A solution of methyl 2-(4-bromophenyl)-2,2-dimethylacetate(3880 muL, 15090 mumol) in EtOH (80 mL) and water (20 mL) was treated with KOH (4233 mg, 75450 mumol). The reaction was heated to 900C. After 15 hours, the reaction was cooled to 23C and concentrated in vacuo. The crude mixture was partitioned between water/diethyl ether (150 mL each). The aqueous layer was separated and extracted with diethyl ether (100 mL). The combined ether layers were then extracted with a IN NaOH solution (25 mL). The combined aqueous washes were acidified with concentrated HCl to pH = 2.0 and extracted with EtOAc (3 x 100 mL). The combined EtOAc layers were dried over MgSO4, and concentrated in vacuo to afford 3144 mg of 2-(4- bromophenyl)-2-methylpropanoic acid.

Reference： [1]Patent: US2010/197591,2010,A1 .Location in patent: Page/Page column 16
[2]Patent: WO2005/19161,2005,A1 .Location in patent: Page/Page column 65
[3]Patent: WO2008/76427,2008,A2 .Location in patent: Page/Page column 125

8
trans-4-aminoadamantan-1-carboxylic acid methyl ester hydrochloride [ No CAS ]
[ 32454-35-6 ]
E-4-[2-(4-bromo-phenyl)-2-methyl-propionylamino]-adamantane-1-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	A solution of the product of Example 22B (3.3 g, 13.5 mmoles), the product of Example 1C (3.3 g, 13.5 mmoles), O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium tetrafluoroborate (8.6 g, 26.9 mmoles) and N,N-diisopropylethylamine (9.4 ml, 53.8 mmoles) in N,N-dimethylformamide (150.0 ml) was stirred at room temperature for about 16 hours under a nitrogen atmosphere. The solvent was evaporated in vacuum and the residue was purified by flash column chromatography on silica gel using hexanes/ethyl acetate (2:1) as the mobile phase to provide the title compound.

Reference： [1]Patent: US2006/149070,2006,A1 .Location in patent: Page/Page column 31

9
[ 32454-36-7 ]
[ 32454-35-6 ]

Yield	Reaction Conditions	Operation in experiment
	With methanol; sodium hydroxide; water; In tetrahydrofuran; at 20℃; for 16h;	To a solution of the product of Example 22A (3.7 g, 13.6 mmoles) in tetrahydrofuran (110.0 ml) and methanol (37.0 ml) was added 2 N sodium hydroxide (19.0 ml) and the solution was stirred at ambient temperature for about 16 hours. The reaction mixture was concentrated in vacuum down to the water layer, was cooled with an ice bath, and was acidified by addition of 2N hydrochloric acid. The precipitate was filtered off and was dried in vacuum to provide the title compound.
		A 100 mL round-bottom flask was charged with <strong>[32454-36-7]ethyl 2-(4-bromophenyl)-2-methylpropanoate</strong> (0.670 g, 2.47 mmol) in 2.5 mL of MeOH. Potassium hydroxide (2.0 M, 2.47 mL, 4.94 mmol) was added at 0 C. The reaction was heated to reflux for 2 h. After cooling the reaction was extracted with ethyl acetate. The aqueous layer was acidified with 2M HCl and extracted with dichloromethane (3×). The combined organic layers were dried over sodium sulfate, filtered and concentrated to give 464 mg of 2-(4-bromophenyl)-2-methylpropanoic acid as a white solid.

Reference： [1]Patent: US2006/149070,2006,A1 .Location in patent: Page/Page column 31
[2]Patent: US2006/199817,2006,A1 .Location in patent: Page/Page column 48

10
[ 10519-96-7 ]
[ 154825-97-5 ]
[ 32454-35-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In tetrahydrofuran;	EXAMPLE 3 Methyl 3-fluoro-4'-{1-methyl-1-[({1-[(trifluoroacetyl)amino]cyclopropyl}-carbonyl)amino]ethyl}-1,1'-biphenyl-2-carboxylate Methyl 2-(4-bromophenyl)-2-methylpropanoate (3.75 g, 14.6 mmol, prepared according to J. Org. Chem., 59:2620-2622(1994)) in 150 mL of THF was allowed to react with <strong>[10519-96-7]potassium trimethylsilanolate</strong> (2.62 g, 20.4 mmol) at ambient temperature, for 60 hours, with continuous stirring. The reaction was then diluted with water and DCM. The pH of the aqueous phase was then adjusted to ca. 4, using 1M HCl. The aqueous layer was then extracted three times with additional DCM. The organic layers were pooled, dried over sodium sulfate, filtered and then concentrated to obtain 3.59 g of 2-(4-bromophenyl)-2-methylpropanoic acid, as a white solid, which gave LC/MS and proton NMR spectra consistent with theory.

Reference： [1]Patent: US2003/220375,2003,A1

11
[ 32454-35-6 ]
[ 73183-34-3 ]
[ 909187-36-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 80℃; for 18h;	A 100 mL round-bottom flask was charged with <strong>[32454-35-6]2-(4-bromophenyl)-2-methylpropanoic acid</strong> (0.48 g, 2.0 mmol), bis(pinacolato)diboron (0.75 g, 3.0 mmol), dichloro[1,1'-bis(diphenylphosphino)ferrocene]dichloride palladium(ii) dichloromethane adduct (0.14 g, 0.20 mmol) and potassium acetate (0.62 mL, 9.9 mmol) in 10 mL of dioxane. The mixture was heated to 80 C. for 18 h, then cooled and concentrated. The residue was dissolved in ethyl acetate and 2 M HCl and filtered. The aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to give 1.34 g of a red solid. The crude material was purified by column chromatography (1/1 ethyl acetate/hexane) to give 525 mg of 2-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoic acid as an off-white solid. ES+=291.2 (M+H).

Reference： [1]Patent: US2006/199817,2006,A1 .Location in patent: Page/Page column 48

Yield	Reaction Conditions	Operation in experiment
		(a) 2-(4-Bromophenyl)-2-methylpropionic acid The ethyl ester of the title compound had been prepared by the method described in J. Am. Chem. Soc: 93, 6877-87 (1971). This ester (54.1 g) was refluxed in a solution of ethanol (50 mL) and NaOH (40 g) in H2 O (400 mL) for 5 hours. The mixture was cooled to ambient temperature, washed with pentane and then acidified with concentrated HCl (100 mL). This precipitated 2-(4-bromophenyl)-2-methylpropionic acid as a white powder, mp 121-124 C., whose NMR was consistent with the structure indicated.

13
[ 32454-35-6 ]
[ 1040860-77-2 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; for 2h;Heating / reflux;	A solution of <strong>[32454-35-6]2-(4-bromophenyl)-2-methylpropanoic acid</strong> (3144 mg, 12933 mumol) in thionyl chloride (9434 muL, 129331 mumol) was heated at reflux under nitrogen. After 2 hours, the reaction was cooled to 23C and concentrated in vacuo to afford the crude acid chloride.

Reference： [1]Patent: WO2008/76427,2008,A2 .Location in patent: Page/Page column 125

14
[ 288-36-8 ]
[ 32454-35-6 ]
[ 1236409-17-8 ]

Yield	Reaction Conditions	Operation in experiment
43%		To a solution of <strong>[32454-35-6]2-(4-bromophenyl)-2-methylpropanoic acid</strong> (9.9 g, 40.7 mmol) and dimethylformamide (0.1 g) in dichloromethane (150 mL) was added oxalyl chloride (4.5 mL, 53 mmol) at room temperature for 2 hours. Reaction concentrated and the residue dissolved in sulfolane (125 mL). 1,2,3-Triazole (3.1 g, 44.8 mmol) and potassium carbonate (11.8 g, 85.6 mmol) were added and the mixture heated 120 C. for 1 hour. The reaction was cooled, diluted with ethyl acetate and washed with 1:1 brine/water (6*600 mL). The organic phase was dried over magnesium sulfate and concentrated. Crude was purified by chromatography on silica eluding with 25% ethyl acetate in hexanes to give 2-(2-(4-bromophenyl)propan-2-yl)oxazole (4.9 g, 43%). 1H NMR (300 MHz, CDCl3): delta ppm 7.55 (s, 1H), 7.41 (dd, 2H), 7.11 (dd, 2H), 1.75 (s, 6H) ppm. (1L): 1H NMR (400 MHz, CDCl3): delta ppm 7.55 (d, J=0.9 Hz, 1H), 7.31-7.24 (m, 4H), 7.06 (d, J=0.9 Hz, 1H), 3.95 (s, 3H), 3.92 (t, J=6.9 Hz, 2H), 3.03 (t, J=6.9 Hz, 2H), 1.79 (s, 6H) ppm. m/z (M+1)=380.0

Reference： [1]Patent: US2010/197591,2010,A1 .Location in patent: Page/Page column 16

15
[ 32454-35-6 ]
C₂₄H₃₄O₃Si [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4150 - 4154

16
[ 32454-35-6 ]
[ 1322094-75-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4150 - 4154

17
[ 32454-35-6 ]
[ 1322094-76-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4150 - 4154

18
[ 1634-04-4 ]
[ 32454-35-6 ]
[ 154825-97-5 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sulfuric acid;Reflux;	General procedure: To a well-stirred mixture of acid (80 mmol) in TBME (50 mL) was added sulfuric acid (1.8 g, 1 mL) at room temperature and refluxed for 16-18 h. The reaction mixture was cooled and added to 20% sodium carbonate solution (100 mL). The reaction mass was extracted in dichloromethane (50 mL × 2). The combined organic layer was washed with water (100 mL), dried over sodium sulfate, and concentrated under reduced pressure to obtain methyl ester (73-97%) as the only product. Most examples gave NMR pure product. Where minor impurities were formed, the product was purified over silica gel using ethyl acetate: petroleum ether (1:9).

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 4262 - 4265

19
[ 32454-35-6 ]
[ 1365091-34-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853
[2]Patent: WO2012/116151,2012,A2

20
[ 32454-35-6 ]
[ 1365091-28-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853
[2]Patent: WO2012/116151,2012,A2

21
[ 32454-35-6 ]
[ 1365091-35-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853
[2]Patent: WO2012/116151,2012,A2

22
[ 32454-35-6 ]
[ 1365091-26-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853
[2]Patent: WO2012/116151,2012,A2

23
[ 32454-35-6 ]
[ 1365091-27-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853
[2]Patent: WO2012/116151,2012,A2
[3]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

24
[ 32454-35-6 ]
[ 1365091-29-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853
[2]Patent: WO2012/116151,2012,A2

25
[ 32454-35-6 ]
[ 1365091-30-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853
[2]Patent: WO2012/116151,2012,A2
[3]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

26
[ 32454-35-6 ]
[ 1365091-31-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853
[2]Patent: WO2012/116151,2012,A2

27
[ 32454-35-6 ]
[ 1365091-32-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853
[2]Patent: WO2012/116151,2012,A2

28
[ 32454-35-6 ]
[ 1365091-33-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853
[2]Patent: WO2012/116151,2012,A2

29
[ 32454-35-6 ]
[ 871-29-4 ]
[ 1356089-38-7 ]

Yield	Reaction Conditions	Operation in experiment
43%		To a solution of <strong>[32454-35-6]2-(4-bromophenyl)-2-methylpropanoic acid</strong> (2.43 g, 10 mmol) in anhydrous THF (150 ml) under nitrogen at - 80 C (ether/dry ice), was added slowly phenyl lithium in toluene (1.8 M, 11 mmol). After 5 min, to this mixture, n-BuLi (2.5 M in hexane, 11 mmol) was added. A cloudy suspension was slowly formed. Twenty minutes after BuLi addition, a stream of SO2 was bubbled through the mixture for 15 min. The reaction mixture was then allowed to warm up to room temperature and the solvent was removed in vacuo. The sulfinate residue was dissolved in water (15 ml), acetic acid (8 ml), and MeOH (20 ml), followed by addition of 2-chloroacrylonitrile (18 mmol). The resulting mixture was stirred at room temperature overnight. The organic solvents were removed in vacuo and the residue was diluted with 20 ml of water. The solution was adjusted to pH5-6 with sat. K2PO4 aq. solution then extracted with dichloromethane (2x100 ml) and dried over MgSO4. After filtration, the filtrate was stirred with triethylamine (20 mmol) for 1 h. The solution was washed with 10% aq citric acid and brine, then dried over MgSO4. The final product was purified by flash column chromatography (silica gel, dichloromethane/EtOAc, gradient) to give 2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-2-methyl- propionic acid (1.2 g, 43%) as a white solid. 1H-NMR (DMSO-d6, 400 MHz) delta 12.65 (s, 1H), 8.23 (d, 1H, J = 15.6 Hz), 7.88 (m, 2H), 7.68 (m, 2H), 6.91 (d, 1H, J = 15.6 Hz), 1.51 (s, 6H); 13C-NMR: (DMSO-d6, 100 MHz) delta 176.7, 152.4, 149.1, 135.6, 128.2, 127.5, 114.6, 112.0, 46.4, 26.1.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1850 - 1853

30
[ 32454-35-6 ]
N-(4-amino-benzyl)-2-[4-((E)-2-cyano-ethenesulfonyl)-phenyl]-isobutyramide trifluoroacetic acid salt [ No CAS ]

Reference： [1]Patent: WO2012/116151,2012,A2

31
[ 32454-35-6 ]
[ 1394819-27-2 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

32
[ 32454-35-6 ]
[ 1394819-28-3 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

33
[ 32454-35-6 ]
[ 1394819-29-4 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

34
[ 32454-35-6 ]
[ 1394819-30-7 ]

Reference： [1]Patent: WO2012/116151,2012,A2

35
[ 32454-35-6 ]
[ 1394819-31-8 ]

Reference： [1]Patent: WO2012/116151,2012,A2

36
[ 32454-35-6 ]
[ 1394819-32-9 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

37
[ 32454-35-6 ]
[ 1394819-33-0 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

38
[ 32454-35-6 ]
[ 1394819-34-1 ]

Reference： [1]Patent: WO2012/116151,2012,A2

39
[ 32454-35-6 ]
(E)-3-{4-[1-methyl-1-(5-phenylamino-[1,3,4]oxadiazol-2-yl)-ethyl]-benzenesulfonyl}-acrylonitrile trifluoroacetic acid salt [ No CAS ]

Reference： [1]Patent: WO2012/116151,2012,A2

40
[ 32454-35-6 ]
(E)-3-{4-[1-(5-Ethylamino-[1,3,4]oxadiazol-2-yl)-1-methyl-ethyl]-benzenesulfonyl}-acrylonitrile trifluoroacetic acid salt [ No CAS ]

Reference： [1]Patent: WO2012/116151,2012,A2

41
[ 32454-35-6 ]
[ 1394819-39-6 ]

Reference： [1]Patent: WO2012/116151,2012,A2

42
[ 32454-35-6 ]
(E)-3-{4-[1-methyl-1-(5-methyl-benzoxazol-2-yl)-ethyl]-benzenesulfonyl}-acrylonitrile trifluoroacetic acid salt [ No CAS ]

Reference： [1]Patent: WO2012/116151,2012,A2

43
[ 32454-35-6 ]
[ 1394819-43-2 ]

Reference： [1]Patent: WO2012/116151,2012,A2

44
[ 32454-35-6 ]
[ 1394819-45-4 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

45
[ 32454-35-6 ]
[ 1394819-57-8 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

46
[ 32454-35-6 ]
[ 1394819-59-0 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

47
[ 32454-35-6 ]
[ 1394818-97-3 ]

Reference： [1]Patent: WO2012/116151,2012,A2

48
[ 32454-35-6 ]
[ 1394819-60-3 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

49
[ 32454-35-6 ]
[ 1394819-61-4 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

50
[ 32454-35-6 ]
[ 1394819-66-9 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

51
[ 32454-35-6 ]
[ 1394819-68-1 ]

Reference： [1]Patent: WO2012/116151,2012,A2

52
[ 32454-35-6 ]
[ 1394819-44-3 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

53
[ 32454-35-6 ]
[ 1394819-77-2 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

54
[ 32454-35-6 ]
C₁₀H₁₀O₄S^(2-)*2Li⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 12-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-2-methyl- propionic acidTo a solution of <strong>[32454-35-6]2-(4-bromophenyl)-2-methylpropanoic acid</strong> (2.43 g, 10 mmol) in anhydrous THF (150 ml) under nitrogen at - 80 C (ether/dry ice), was added slowly phenyl lithium in toluene (1.8 M, 11 mmol). After 5 min, to this mixture, n-BuLi (2.5 M hexane, 11 mmol) was added. A cloudy suspension was slowly formed. Twenty minutes after BuLi addition, a stream of S02 was bubbled through the mixture for 15 min. The reaction mixture was then allowed to warm up to room temperature and the solvent was removed in vacuo. The sulfmate residue was dissolved in water (15 ml), acetic acid (8 ml), and MeOH (20 ml), followed by addition of 2-chloroacrylonitrile (18 mmol). The resulting mixture was stirred at room temperature overnight. The organic solvents were removed in vacuo and the residue was diluted with 20 ml of water. The solution was adjusted to pH5-6 with sat. K2HP04 aq. solution then extracted with dichloromethane (2x100 ml) and dried over MgS04. After filtration, the filtrate was stirred withtriethylamine (20 mmol) for 1 h. The solution was washed with 10% aq citric acid and brine, and then dried over MgS04. The final product was purified by flash column chromatography (silica gel, dichloromethane/EtOAc, gradient) to give 2-[4-((E)-2-Cyano- ethenesulfonyl)-phenyl]-2 -methyl- propionic acid (1.2 g, 43%) as a white solid. 1H-NMR (DMSO-d6, 400 MHz) delta 12.65 (s, 1H), 8.23 (d, 1H, J = 15.6 Hz), 7.88 (m, 2H), 7.68 (m, 2H), 6.91 (d, 1H, J = 15.6 Hz), 1.51 (s, 6H); 13C-NMR: (DMSO-d6, 100 MHz) delta 176.7, 152.4, 149.1, 135.6, 128.2, 127.5, 114.6, 112.0, 46.4, 26.1.

Reference： [1]Patent: WO2012/116151,2012,A2 .Location in patent: Page/Page column 35-36

55
[ 32454-35-6 ]
[ 1394818-98-4 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

56
[ 32454-35-6 ]
[ 1394819-01-2 ]

Reference： [1]Patent: WO2012/116151,2012,A2

57
[ 32454-35-6 ]
[ 1394819-02-3 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

58
[ 32454-35-6 ]
[ 1394819-03-4 ]

Reference： [1]Patent: WO2012/116151,2012,A2

59
[ 32454-35-6 ]
[ 1394819-04-5 ]

Reference： [1]Patent: WO2012/116151,2012,A2

60
[ 32454-35-6 ]
[ 1394819-05-6 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

61
[ 32454-35-6 ]
[ 1394819-06-7 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

62
[ 32454-35-6 ]
[ 1394819-07-8 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

63
[ 32454-35-6 ]
[ 1356089-38-7 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

64
[ 32454-35-6 ]
[ 1394819-08-9 ]

Reference： [1]Patent: WO2012/116151,2012,A2

65
[ 32454-35-6 ]
2-[4-((E)-2-cyano-ethenesulfonyl)-phenyl]-N-(4-pyrazol-1-yl-benzyl)-isobutyramide trifluoroacetic acid salt [ No CAS ]

Reference： [1]Patent: WO2012/116151,2012,A2

66
[ 32454-35-6 ]
[ 1394819-11-4 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

67
[ 32454-35-6 ]
[ 1394819-12-5 ]

Reference： [1]Patent: WO2012/116151,2012,A2

68
[ 32454-35-6 ]
[ 1394819-13-6 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

69
[ 32454-35-6 ]
[ 1394819-14-7 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

70
[ 32454-35-6 ]
[ 1394819-15-8 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

71
[ 32454-35-6 ]
[ 1394819-16-9 ]

Reference： [1]Patent: WO2012/116151,2012,A2

72
[ 32454-35-6 ]
[ 1394819-17-0 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

73
[ 32454-35-6 ]
[ 1394819-18-1 ]

Reference： [1]Patent: WO2012/116151,2012,A2
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 1140 - 1158

74
[ 32454-35-6 ]
[ 1394819-19-2 ]

Reference： [1]Patent: WO2012/116151,2012,A2

75
[ 32454-35-6 ]
[ 1394819-20-5 ]

Reference： [1]Patent: WO2012/116151,2012,A2

76
[ 32454-35-6 ]
[ 1394819-21-6 ]

Reference： [1]Patent: WO2012/116151,2012,A2

77
[ 32454-35-6 ]
[ 154825-96-4 ]

Reference： [1]Patent: US2012/309973,2012,A1
[2]Patent: EP2532644,2012,A1

78
[ 32454-35-6 ]
[ 83799-24-0 ]

Reference： [1]Patent: US2012/309973,2012,A1
[2]Patent: EP2532644,2012,A1

79
[ 67-56-1 ]
[ 32454-35-6 ]
[ 154825-97-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sulfuric acid; acetonitrile; at 80 - 85℃; for 16 - 18h;	General procedure: To a well-stirred mixture of acid (80 mmol), alcohol (90 mmol), acetonitrile (162 mmol) and sulfuric acid (98%, 94 mmol, 5 mL) was added at room temperature. Slowly heated to 80-85 C and maintained between 80-85C for16-18 h. The reaction mixture was cooled and added to 20% sodium carbonate solution (100mL). The reaction mass was extracted in CH2Cl2 (50 mL × 2). The combined organic layer was washed with water (100 mL), dried over sodium sufate, and concentrated under reduced pressure to obtain corresponding ester (97-99%) as the only product. Most example gave NMR pure product. Where minor impurities are formed, the product was purified over silica gel using ethyl acetate: petroleum ether (1:9).
79%	With sulfuric acid; In toluene; at 63 - 67℃; for 16h;Industry scale;	Step-3: Preparation of methyl 2-(4-bromophenyl)-2-methylpropionate For operational convenience the product from two or three batches of Step-2 are combined and used in this step. The wet material (on dry basis) from step-2 (575 Kg, purity of about 98.2%) was charged into a reactor containing 1150 L of toluene. The mass was maintained for about 15 minutes or until a clear solution was obtained. The toluene layer was washed with sodium chloride solution (20% in water) and separated. To the toluene layer, methanol (300 L) was charged followed by sulphuric acid addition at 25-35 C. The reaction mass temperature was gradually raised to 63-67 C. and stirred for 16 hours or until complete consumption of <strong>[32454-35-6]2-(4-bromophenyl)-2-methylpropanoic acid</strong> as indicated by GC analysis. The mass was gradually cooled to 25-35 C. and then washed with water (3500 L), sodium carbonate solution (2% in water) and sodium chloride (10% solution in water) successively. Organic phase was subjected to distillation under reduced pressure to obtain methyl 2-(4-bromophenyl)-2-methylpropionate (480 Kg, 79% yield, GC purity: 99.2%).
79%	With sulfuric acid; In toluene; at 63 - 67℃; for 16h;Industry scale;	Step-3: Preparation of methyl 2-(4-bromophenyl)-2-methylpropionate: For operational convenience the product from two or three batches of Step-2 are combined and used in this step. The wet material (on dry basis) from step-2 (575 Kg, purity of about 98.2%) was charged into a reactor containing 1150 L of toluene. The mass was maintained for about 15 minutes or until a clear solution was obtained. The toluene layer was washed with sodium chloride solution (20% in water) and separated. To the toluene layer, methanol (300 L) was charged followed by sulphuric acid addition at 25-35C. The reaction mass temperature was gradually raised to 63-67C and stirred for 16 hours or until complete consumption of <strong>[32454-35-6]2-(4-bromophenyl)-2-methylpropanoic acid</strong> as indicated by GC analysis. The mass was gradually cooled to 25-35C and then washed with water (3500 L), sodium carbonate solution (2% in water) and sodium chloride (10% solution in water) successively. The organic phase was subjected to distillation under reduced pressure to obtain methyl 2-(4-bromophenyl)-2-methylpropionate (480 Kg, 79% yield, GC purity: 99.2%).

Reference： [1]Synthetic Communications,2014,vol. 44,p. 836 - 846
[2]Patent: US2012/309973,2012,A1 .Location in patent: Page/Page column 4
[3]Patent: EP2532644,2012,A1 .Location in patent: Page/Page column 6

80
[ 71-43-2 ]
[ 32454-35-6 ]

Reference： [1]Patent: US2012/309973,2012,A1
[2]Patent: EP2532644,2012,A1

81
[ 32454-35-6 ]
[ 1418028-03-1 ]

Yield	Reaction Conditions	Operation in experiment
41%	With isopropylmagnesium bromide; triphenylphosphine; cobalt(II) chloride; In tetrahydrofuran; at 20℃; for 18h;Green chemistry;	General procedure: The iPrMgBr (excess in THF) was added to a mixture of alpha,alpha-dimethyl phenylacetic acids (1 mmol), cobalt salt (10 mol%), ligand (20 mol%) in dried THF (3 mL), the reaction mixture was stirred at room temperature for 18 h. After that, the mixture was concentrated under vacuum and the residue was purified by column chromatography on silica gel with a gradient eluent of petroleum ether and dichloromethane to give the corresponding products.

Reference： [1]Journal of the American Chemical Society,2013,vol. 135,p. 1236 - 1239
[2]Tetrahedron Letters,2020,vol. 61
[3]Patent: WO2018/149419,2018,A1 .Location in patent: Paragraph 00755; 00757

82
[ 53086-53-6 ]
[ 74-88-4 ]
[ 32454-35-6 ]

Reference： [1]Journal of the American Chemical Society,2013,vol. 135,p. 1236 - 1239

83
[ 32454-35-6 ]
[ 1431616-20-4 ]

Reference： [1]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 514 - 516

84
[ 32454-35-6 ]
[ 1431616-22-6 ]

Reference： [1]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 514 - 516

85
[ 32454-35-6 ]
C₁₆H₁₃ClN₂O [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 514 - 516

86
[ 32454-35-6 ]
[ 214973-83-8 ]

Reference： [1]Patent: US2017/137385,2017,A1

87
[ 32454-35-6 ]
[ 2077-19-2 ]

Reference： [1]Nature,2019,vol. 573,p. 398 - 402

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Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

Precautionary Statements-General
Code	Phrase
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P272	Contaminated work clothing should not be allowed out of the workplace.
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P281	Use personal protective equipment as required.
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Response
Code	Phrase
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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. 32454-35-6 ] {[proInfo.proName]}

Quality Control of [ 32454-35-6 ]

Related Doc. of [ 32454-35-6 ]

Product Details of [ 32454-35-6 ]

Calculated chemistry of [ 32454-35-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 32454-35-6 ]

Application In Synthesis of [ 32454-35-6 ]

[ 32454-35-6 ] Synthesis Path-Upstream 1~3

[ 32454-35-6 ] Synthesis Path-Downstream 1~87

Related Functional Groups of [ 32454-35-6 ]

Aryls

Bromides

Carboxylic Acids

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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[ 32454-35-6 ]