[ CAS No. 57625-74-8 ] {[proInfo.proName]}

Name: 57625-74-8|Methyl 2-methyl-2-phenylpropanoate|98%
Brand: Ambeed
SKU: A215824
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2D 3D

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Quality Control of [ 57625-74-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 57625-74-8 ]

Product Details of [ 57625-74-8 ]

CAS No. :	57625-74-8	MDL No. :	MFCD01846451
Formula :	C₁₁H₁₄O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WITYUUTUSPKOAB-UHFFFAOYSA-N
M.W :	178.23	Pubchem ID :	143498
Synonyms :

Calculated chemistry of [ 57625-74-8 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.36
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	51.8
TPSA :	26.3 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) :	-5.51 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.49
Log Po/w (XLOGP3) :	2.64
Log Po/w (WLOGP) :	2.14
Log Po/w (MLOGP) :	2.58
Log Po/w (SILICOS-IT) :	2.42
Consensus Log Po/w :	2.45

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.75
Solubility :	0.316 mg/ml ; 0.00177 mol/l
Class :	Soluble
Log S (Ali) :	-2.84
Solubility :	0.256 mg/ml ; 0.00144 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.29
Solubility :	0.0906 mg/ml ; 0.000508 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.37

Safety of [ 57625-74-8 ]

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

Application In Synthesis of [ 57625-74-8 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 57625-74-8 ]

[ 57625-74-8 ] Synthesis Path-Downstream 1~88

1
[ 57625-74-8 ]
[ 71254-82-5 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1957,vol. 76,p. 297,310

2
[ 57625-74-8 ]
[ 66622-43-3 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1957,vol. 76,p. 297,310

3
[ 80-62-6 ]
[ 71-43-2 ]
[ 57625-74-8 ]

Reference： [1]Patent: US2571639,1949,

4
[ 186581-53-3 ]
[ 826-55-1 ]
[ 57625-74-8 ]

Reference： [1]Bulletin de la Societe Chimique de France,1969,p. 787 - 790
[2]Canadian Journal of Chemistry,1990,vol. 68,p. 1106 - 1115

5
[ 67-56-1 ]
[ 10409-54-8 ]
[ 57625-74-8 ]

Reference： [1]Chemische Berichte,1983,vol. 116,p. 3631 - 3636
[2]Journal of Organic Chemistry,1976,vol. 41,p. 3067 - 3076
[3]Il Farmaco,1999,vol. 54,p. 600 - 610

6
[ 57625-74-8 ]
[ 75-16-1 ]
[ 2371-91-7 ]

Reference： [1]Bulletin de la Societe Chimique de France,1969,p. 787 - 790
[2]Journal of the American Chemical Society,1966,vol. 88,p. 5571 - 5581

7
[ 31508-44-8 ]
[ 74-88-4 ]
[ 57625-74-8 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; ammonium chloride; diisopropylamine; In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide; hexane; water;	REFERENCE EXAMPLE 78 Methyl 2-methyl-2-phenylpropionate (78) STR97 A solution of n-butyl lithium in hexane (1.44N, 60.0 ml, 86.4 mmol) was added to a solution of diisopropylamine (9.07 g, 89.6 mmol) in anhydrous THF (200 ml) cooled at -30 C. under argon atmosphere, and the mixture was stirred for 20 minutes. To this reaction mixture were added a solution of methyl 2-phenylpropionate (10.5 g, 64.0 mmol) in 10 ml of anhydrous THF and HMPA (16.5 g, 92.0 mmol), and the mixture was stirred at -30 C. for 10 minutes and then at 0 C. for 45 minutes. To this reaction solution was added a solution of methyl iodide (13.6 g, 96.0 mmol) in anhydrous THF (30 ml) at -30 C., and the mixture was stirred at -30 C. for 1 hour. This reaction mixture was added to an aqueous saturated solution of ammonium chloride (400 ml) and water (50 ml) was added. The mixture was extracted with ether (400 ml). The aqueous layer further extracted with ethyl acetate. The combined organic layers were washed with water (300 ml) and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was distilled (b.p. 99-100 C./6 mmHg) to give an oil of methyl 2-methyl-2-phenylpropionate (7.63 g, 42.9 mmol, 67.0%). This compound was assigned the structure by the following data: IR(Liquid film method): 2970, 1730, 1600, 1500, 1450, 1390, 1370, 1250, 1190, 1150, 1100, 1080, 1030, 1020, 990, 850, 770, 740, 700 cm-1. NMR(90 MHz, CDCl3, delta): 1.58(6H, s), 3.64(3H, s), 7.1-7.4(5H, m).

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1975,p. 1347 - 1352
[2]Patent: US4775692,1988,A
[3]Chemical Communications,2017,vol. 53,p. 8316 - 8319

8
[ 67-56-1 ]
[ 826-55-1 ]
[ 57625-74-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; at 20℃; for 12h;Heating / reflux;	Methanol (2.5 LTR), 2,2-dimethyl-2-phenyl-acetic acid (Intermediate 1) (0.5 kg), and conc. sulphuric acid (50 ml) were charged to a reactor at room temperature. The temperature was raised to reflux and maintained for 12 hours. The pH was adjusted to 7-8 using aqueous ammonia and the methanol concentrated completely. The reaction mass was quenched in water (1 LTR) and extracted with MDC (750 ml). The MDC layer was dried over sodium sulphate and concentrated to obtain 500 gms of the title compound as an oil having 98% purity
	With sulfuric acid; at 25 - 45℃; for 4h;Heating / reflux;	(a) Reaction of alpha,alpha-Dimethyl phenyl acetic acid and methanol alpha,alpha-Dimethylphenyl acetic acid was reacted with methanol in presence of cone, sulfuric acid between about 25 to 45C. Reaction mixture was refluxed for about 4 hours. Methanol was distilled off after the said time to give thick oily slurry of Methyl-alpha,alpha-dimethylphenyl acetic acid. Water was added to the pre-cooled reaction mixture and extracted with chloroform EPO <DP n="8"/>followed by washing with aqueous sodium bicarbonate solution and finally with potable water. Removal of chloroform under reduced pressure yielded title compound as oily mass in about 98 % HPLC purity.EXAMPLE 1Methyl- a, a-Dimethyl phenyl acetate (ester)51 Kg (0.3109 Kmole) of alpha,alpha-Dimethyl acetic acid was dissolved in 100 to 150 Ltr methanol and to it was added concentrated sulfuric acid, 6 to 9 Kg maintaining temperature 25 to 450C. After complete addition of sulfuric acid reaction mixture was refluxed for 4 hours. After completion of the reaction methanol was distilled off under vacuum to obtain thick slurry which was cooled to room temperature and to it was added water. Reaction mixture was then extracted with chloroform and washed with 10% w/v sodium bicarbonate aqueous solution. Finally, chloroform layer was washed with potable water. On removal of chloroform under vacuum, Methyl-alpha,alpha-Dimethyl phenyl acetate as oily mass was obtained. HPLC Purity = 98%. Yield = 40 to 50 Kg
1 g	With methanesulfonic acid; for 2h;Sealed tube; Reflux;	A 100 mL sealed tube was charged with intermediate 39b (1.6 g, 9.7 mmol) and methanol (10 mL). To the above stirred solution CH3SO3H (1 .6 mL) was added drop wise and refluxed for 2 h. The reaction mixture concentrated and was diluted with ice- water and neutralized with NaHCO3, extracted with ethyl acetate, washed with water and dried. The product was obtained by concentrating under vacuo, which was further purified by combiflash to yield the title compound (1 .0 g) as a colourless liquid.H NMR: (ODd3, 300MHz) 6 7.25-7.27(d, 4H) 7.17-7.20 (m, 1H), 3.58 (5, 3H),1 .51 (5, 6H).

2 g

With sulfuric acid; at 0℃;Reflux;

To a stirred solution of 2-methyi-2-phenyipropanoic acid (2 g, 12.18 mmol) in methanol (30m1) at 0 was added drop wise solution of H2S04 (2 ml, 37.5 mmol), The reaction mixture was heated torefiux for overnight. After completion of reaction, methanol was evaporated under reduced pressure and the residue was diluted with dichioromethane. The organic portion was washed with saturatedsodium bicarbonate solution, brine and evaporated under reduced pressure to give methyl 2-methyl-2-phenyipropanoate (2 g) as oil.

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2011,vol. 54,p. 352 - 356
[2]Journal of Organic Chemistry,1994,vol. 59,p. 2792 - 2798
[3]Patent: WO2005/19175,2005,A1 .Location in patent: Page/Page column 23
[4]Patent: WO2007/7347,2007,A1 .Location in patent: Page/Page column 4; 6-7; 10
[5]Patent: WO2014/202528,2014,A1 .Location in patent: Page/Page column 107; 108
[6]Patent: WO2018/116072,2018,A1 .Location in patent: Page/Page column 75; 76; 79

9
[ 67-56-1 ]
[ 10409-54-8 ]
[ 59671-36-2 ]
[ 57625-74-8 ]

Reference： [1]Synthesis,1985,p. 436 - 437

10
[ 67-56-1 ]
[ 36293-05-7 ]
[ 57625-74-8 ]

Reference： [1]Journal of the American Chemical Society,1986,vol. 108,p. 4119 - 4125

11
[ 57625-74-8 ]
[ 826-55-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With water; sodium hydroxide; In 1,4-dioxane; for 24h;	Methyl 2-methyl-2-phenylpropanoate (0.840 g, 4.71 mmol) was dissolved in 5 mL of l,4-dioxane and 10 mL of 1.0 M NaOH (10.0 mmol, 2.1 equiv) was added. The mixture was heated at 95 C for 24 h. 20 mL of 1.0 M HC1 was added and the mixture was extracted with dichloromethane (3 x 20 mL). Combined organic fractions were washed with brine (30 mL), filtered through cotton and concentrated under reduced pressure to yield a crude mixture which was purified by flash chromatography (hexanes/ethyl acetate), 0.758 g of 2-methyl-2-phenylpropanoic acid (4.62 mmol, 98%).
89 g	With water; sodium hydroxide; In methanol; at 10℃; for 3h;Reflux;	Example-l: Preparation of 2-methyl-2-phenylpropanoic acid (FormuIa-3) Methyl 2-methyl-2-phenylpropanoate compound of formula-2 (100 gm) and methanol (500 ml) were added to a pre-cooled mixture of sodium hydroxide (45 gm) and water (500 ml) at 10-15C. Heated the reaction mixture to reflux temperature and stirred for 3 hrs at the same temperature. Distilled off the solvent completely from the reaction mixture under reduced pressure and cooled the reaction mixture to 25-30C. Water was added to the reaction mixture and cooled to 5-10C. Acidified the reaction mixture using dil.HCl solution at 5-10C. Raised the temperature of the reaction mixture to 25-30C and stirred for 30 rhin at the same temperature. Filtered the solid, washed with water and dried the material to get the title compound. Yield: 89.0 gm.
	With water; sodium hydroxide; In methanol; at 65℃;	General procedure: The ester II was added to a mixture of NaOH (2.0 M, 8 mL) and methanol (10 mL)and stirred overnight at 65 C. After removal of methanol in vacuo, the residue wasdiluted with water and extracted with EtOAc (10 mL × 3). Then the pH value of thewater layer was adjusted to 2.0 with HCl (2.0 M) and extracted with EtOAc (30 mL ×3). The combined organic phases were evaporated in vacuo to give the crudecarboxylic acid III, which was used directly for the next step without furtherpurification.

Reference： [1]Patent: WO2019/99760,2019,A1 .Location in patent: Paragraph 0055; 0058
[2]Synthesis,1985,p. 436 - 437
[3]Il Farmaco,1999,vol. 54,p. 600 - 610
[4]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3887 - 3890
[5]Patent: WO2014/188453,2014,A2 .Location in patent: Page/Page column 22
[6]Chemical Communications,2017,vol. 53,p. 8316 - 8319
[7]Chinese Chemical Letters,2018,vol. 29,p. 191 - 193

12
[ 71254-82-5 ]
[ 3461-39-0 ]
[ 2438-04-2 ]
[ 57625-74-8 ]
[ 71302-96-0 ]
[ 66164-33-8 ]
[ 129976-23-4 ]

Reference： [1]Canadian Journal of Chemistry,1990,vol. 68,p. 1106 - 1115

13
[ 140-29-4 ]
[ 616-38-6 ]
[ 57625-74-8 ]
[ 1823-91-2 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 1323 - 1328

14
[ 84782-16-1 ]
[ 3461-39-0 ]
[ 57625-74-8 ]

Reference： [1]Journal of Organic Chemistry,1990,vol. 55,p. 5037 - 5041

15
[ 84782-16-1 ]
[ 29393-16-6 ]
[ 57625-74-8 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1982,vol. 55,p. 3939 - 3940
[2]Journal of the American Chemical Society,1988,vol. 110,p. 3112 - 3120
[3]Journal of the American Chemical Society,1988,vol. 110,p. 3112 - 3120

16
[ 71254-83-6 ]
[ 3461-39-0 ]
[ 2438-04-2 ]
[ 31508-44-8 ]
[ 57625-74-8 ]
[ 71254-87-0 ]
[ 71254-85-8 ]

Reference： [1]Canadian Journal of Chemistry,1990,vol. 68,p. 1106 - 1115

17
N-[1-Methoxy-2-methyl-2-phenyl-prop-(Z)-ylidene]-4-methyl-benzenesulfonamide [ No CAS ]
[ 57625-74-8 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1992,vol. 28,p. 1229 - 1230
Zhurnal Organicheskoi Khimii,1992,vol. 28,p. 1546 - 1548

18
[ 23981-48-8 ]
[ 616-38-6 ]
[ 57625-74-8 ]
[ 30012-51-2 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 1323 - 1328

19
[ 616-38-6 ]
[ 101-41-7 ]
[ 31508-44-8 ]
[ 57625-74-8 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 1323 - 1328

20
[ 67-56-1 ]
[ 611-70-1 ]
[ 149-73-5 ]
[ 57625-74-8 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1982,p. 235 - 242

21
[ 57625-74-8 ]
[ 74-88-4 ]
[ 2371-91-7 ]

Reference： [1]Journal of the American Chemical Society,1986,vol. 108,p. 4119 - 4125

22
[ 57625-74-8 ]
[ 113-00-8 ]
[ 57486-92-7 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1975,vol. 25,p. 1477 - 1482

23
[ 57625-74-8 ]
[ 2173-69-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 3h;	Methyl 2-methyl-2-phenylpropanoate (10.8 g, 60.6 mmol, Eq: 1.00) in tetrahydrofuran (193 ml) was cooled to 0 C., lithium aluminium hydride was added (30.3 ml, 60.6 mmol, Eq: 1.00) via a syringe over 5 minutes. The mixture was stirred at 0 C. for 3 hours, and 2.3 ml water was added over 2 minutes. The mixture was stirred for 10 minutes, 2.3 ml 1N NaOH was added, the mixture was stirred for 5 minutes (a gel forms), 7 ml water was added, the mixture was stirred for 15 minutes, filtered through a pad of celite. The celite was washed with ether and the solvent was removed under vacuum to give methyl-2-phenyl-propan-1-ol (51) (9.0 g, 99%) as a clear oil. [0351] 1H NMR (400 MHz, dimethyl sulfoxide-d6) delta ppm 1.23 (s, 6H) 3.43 (d, J=5.27 Hz, 2H) 4.66 (t, J=5.27 Hz, 1H) 7.06-7.51 (m, 5H).
	With sodium tetrahydroborate; In tetrahydrofuran; at 20℃; for 5h;	Methyl-2,2-dimethyl-2-phenyl acetate (Intermediate 2) (0.5 kg), and THF (2.5 LTR) were charged to a reactor, and sodium borohydride (100 gms) was added in lots. The mixture was stirred at room temperature for 5 hours. After completion of the reaction, the pH was adjusted to 3-4 with HC1, the inorganics filtered and the filtrate concentrated and stripped with toluene (50 ml) to obtain the title compound as an oil weighing 400 gms.
3.8 g (81%)	With aq NaOH; In water;	Part B. Preparation of 2,2-(Dimethyl)-2-phenylethyl alcohol. To a cooled (0 C.) solution of 1M lithium aluminum hydride in ether (31.1 mL, 31.1 mmol) was added methyl 2,2-(dimethyl)-2-phenylacetate (5.54 g, 31.1 mmol) as a solution in ether. The reaction mixture was allowed to warm to 25 C. and was stirred for 3 h. The mixture was cooled to 0 C. and was quenched by slow sequential addition of 1.2 mL of water, 1.2 mL of 15% aq NaOH and 3.6 mL of water. The resulting slurry was stirred vigorously with warming to 25 C. for 1 h, and then was dried (MgSO4), filtered and concentrated to afford 3.8 g (81%) of the title compound.

Reference： [1]Patent: US2014/194431,2014,A1 .Location in patent: Paragraph 0349-0351
[2]Journal of labelled compounds and radiopharmaceuticals,2011,vol. 54,p. 352 - 356
[3]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 301 - 306
[4]Il Farmaco,1999,vol. 54,p. 600 - 610
[5]Patent: WO2005/19175,2005,A1 .Location in patent: Page/Page column 23-24
[6]Patent: US6060462,2000,A

24
[ 101-41-7 ]
[ 74-88-4 ]
[ 57625-74-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydride; In tetrahydrofuran; mineral oil; at 0 - 20℃; for 24h;	A solution of methyl 2-phenylacetate (2.01 g, 13.4 mmol) and methyl iodide (2.08 mL, 33.5 mmol, 2.5 equiv) in anhydrous THF (15 mL) was treated portionwise with sodium hydride (60% suspension in mineral oil, 1.18 g, 29.5 mmol, 2.2 equiv) at 0 C, warmed to room temperature and reacted for 24 h. The reaction mixture was transferred into a separatory funnel with ice/water and acidified with 1.0 M HC1 (30 mL). The product was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed brine (30 mL), filtered through cotton, and concentrated under reduced pressure to yield dark oil which was purified by flash chromatography (hexanes/ethyl acetate) to provide 2.26 g of methyl 2-methyl-2-phenylpropanoate, yellow oil (12.7 mmol, 95%).
85%		EXAMPLE 9A Methyl 2-methyl-2-phenylpropanoate A solution of methyl 2-phenylacetate (10.0 g, 66.7 mmol) and methyl iodide (10.4 mL, 167 mmol) in tetrahydrofuran (67 mL) at 0 C. was treated portionwise with sodium hydride (5.9 g of 60% in oil, 147 mmol), warmed to 25 C., stirred at 25 C. for 18 hours, cooled to 0 C. and quenched by addition of glatial acetic acid (2 mL). The mixture was concentrated in vacuo. A solution of the residue in ethyl acetate was washed with water, saturated sodium bicarbonate solution (2*) and saturated sodium chloride solution, dried (Na2SO4), filtered and concentrated in vacuo to afforded an oil which was distilled (70-750C/0.3 mm Hg) to afford the title compound (10 g, 85%). 1H NMR (300 MHz, CDCl3): delta 7.27 (m, 5H), 3.65 (s, 3H), 1.60 (m, 6H).
85%		A solution of methyl 2-phenylacetate (10.0 g, 66.7 mmol) and methyl iodide (10.4 mL, 167 mmol) in tetrahydrofuran (67 mL) at 0C was treated portionwise with sodium hydride (5.9 g of 60% in oil, 147 mmol), warmed to 25C, stirred at 25C for 18 hours, cooled to 0C and quenched by addition OF GLATIAL acetic acid (2 mL). The mixture was concentrated in vacuo. A solution of the residue in ethyl acetate was washed with water, saturated sodium bicarbonate solution (2 x) and saturated sodium chloride solution, dried (Na2SO4), filtered and concentrated in vacuo to afforded an oil which was distilled (70-75C/0. 3 mm Hg) to afford the title compound (10 g, 85%). 'H NMR (300 MHz, CDC13) : 8 7.27 (m, 5 H), 3.65 (s, 3 H), 1.60 (m, 6 H).

63%		6.3.1 Methyl-2-methyl-2-phenylpropanoate (2a) Colourless oil. Yield: 7.5 g (63%). 1H NMR (400 MHz, CDCl3): delta 1.63 (s, 6H, CH3), 3.67 (s, 3H, OCH3), 7.30-7.36 (m, 5H, Ar-H). Anal. Calcd. for C11H14O2: C, 74.13; H, 7.92. Found: C, 73.93; H, 7.72.
	With sodium chloride; In water; N,N-dimethyl-formamide;	REFERENCE EXAMPLE 122 STR158 A solution of methyl phenylacetate (7.50 g) and 60% sodium hydride (2.1 g) in N,N-dimethylformamide (70 ml) was stirred for one hour at room temperature. To the resultant mixture was dropwise added methyl iodide (10 g) under ice cooling and stirred for 3 hours at 50 C. After cooling, the resultant crystals were filtered off. To the filtrate was added 60% sodium hydride (2.1 g) and then the resultant mixture was treated as mentioned above Again, to the resultant filtrate was added 60% sodium hydride (0.4 g) and the mixture was heated for one hour at 50 C. To the mixture was added methyl iodide (2.0 g) under ice cooling and stirred for 15 hours. After adding dropwise water to the reaction solution under ice cooling, the solution was concentrated under reduced pressure. To the residue was added water and the mixture was extracted with ether. After washing twice with water, the ether layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue thus obtained was subjected to silica gel column chromatography (200 g). Elution with a hexane-ethyl acetate (10:1) mixture gave 8.04 g of methyl 2-methyl-2-phenylpropionate. NMR (CDCl3): 1.60 (6H,s), 3.68(3H,s) 7.35(5H,br.s)
		Step B. To a mixture of methyl phenylacetate (150.0 mg, 1.0 mmol) in THFat-78 C was addedNaHMDS(2. 2 ml, 2.2mmol). After stirring at this temperature for 15 min, MeI (312.0 mg, 2.2 mmol) was added to the above mixture. The resulted mixture was stirred at-78 C for 3 hr and rt for 1 hr. The mixture was cooledto-78 C, quenched with sat'dNH4C1, diluted with EtOAc, washed with aq.NaHCO3 and brine, and dried. Flash chromatography purification(10% EtOAc in hexane) gave 2-methyl-2-phenyl-propionic acid methyl ester as clear oil. MS found: (M+1) +=179.1.

Reference： [1]Patent: WO2019/99760,2019,A1 .Location in patent: Paragraph 0055; 0057
[2]Patent: US2005/107364,2005,A1 .Location in patent: Page/Page column 71
[3]Patent: WO2005/19191,2005,A2 .Location in patent: Page/Page column 141
[4]Journal of Heterocyclic Chemistry,2011,vol. 48,p. 998 - 1005
[5]European Journal of Medicinal Chemistry,2012,vol. 57,p. 407 - 416
[6]RSC Advances,2015,vol. 5,p. 96851 - 96854
[7]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 301 - 306
[8]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285
[9]Patent: US4987132,1991,A
[10]Patent: WO2003/99276,2003,A1 .Location in patent: Page 438

25
[ 7446-70-0 ]
[ 80-62-6 ]
[ 71-43-2 ]
[ 57625-74-8 ]

Reference： [1]Patent: US2571639,1949,

27
[ 826-55-1 ]
methanol. H₂SO₄ [ No CAS ]
[ 57625-74-8 ]

Reference： [1]Journal of Organic Chemistry,1958,vol. 23,p. 1469,1472

28
[ 98-83-9 ]
paraformaldehyde [ No CAS ]
[ 3461-39-0 ]
[ 16251-77-7 ]
[ 2722-36-3 ]
[ 57625-74-8 ]

Reference： [1]Tetrahedron Letters,1982,vol. 23,p. 4967 - 4968

29
[ 57625-74-8 ]
[ 5809-15-4 ]

Yield	Reaction Conditions	Operation in experiment
73%	With hydrazine; In ethanol; for 6h;Reflux;	6.4.1 2-Methyl-2-phenylpropanehydrazide (3a) Off white solid. Yield: 7.2 g (73%); m.p.: 76.5-77.4 C. 1H NMR (400 MHz, CDCl3): delta 1.60 (s, 6H, CH3), 3.80 (s, 2H, -NH2), 6.50 (s, 1H, -NH-), 7.27-7.37 (m, 5H, Ar-H). UPLC 180.2 (M + H)+. Anal. Calcd. for C10H14N2O: C, 67.39; H, 7.92; N, 15.72. Found: C, 67.79; H, 8.22; N, 15.97.

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285
[2]Journal of Heterocyclic Chemistry,2011,vol. 48,p. 998 - 1005
[3]European Journal of Medicinal Chemistry,2012,vol. 57,p. 407 - 416

30
[ 108-86-1 ]
[ 547-63-7 ]
[ 57625-74-8 ]

Reference： [1]Journal of the American Chemical Society,2002,vol. 124,p. 12557 - 12565

31
[ 108-86-1 ]
[ 31469-15-5 ]
[ 57625-74-8 ]

Reference： [1]Journal of the American Chemical Society,2003,vol. 125,p. 11176 - 11177
[2]Journal of the American Chemical Society,2004,vol. 126,p. 5182 - 5191

32
[ 611-70-1 ]
[ 149-73-5 ]
[ 57625-74-8 ]

Reference： [1]Journal of Chemical Research,2004,p. 392 - 393

33
[ 67-56-1 ]
[ 201230-82-2 ]
[ 98-83-9 ]
[ 3461-39-0 ]
[ 57625-74-8 ]

Reference： [1]Organic Letters,2006,vol. 8,p. 6143 - 6145
[2]Applied Organometallic Chemistry,2014,vol. 28,p. 364 - 371

34
[ 50407-04-0 ]
[ 57625-74-8 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1992,vol. 28,p. 1229 - 1230
Zhurnal Organicheskoi Khimii,1992,vol. 28,p. 1546 - 1548

35
[ 57625-74-8 ]
2-[5-amino-2-(4-fluoro-phenyl)-6-oxo-6H-pyrimidin-1-yl]-N-{2-methyl-1-[5-(1-methyl-1-phenyl-ethyl)-[1,3,4]oxadiazole-2-carbonyl]-propyl}-acetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

36
[ 57625-74-8 ]
[ 252253-32-0 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

37
[ 57625-74-8 ]
[ 337969-19-4 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

38
[ 57625-74-8 ]
(2S)-2-amino-3-methyl-1-[5-(1-methyl-1-phenylethyl)-1,3,4-oxadiazol-2-yl]butan-1-ol hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

39
[ 57625-74-8 ]
2-[6-oxo-2-(4-fluorophenyl)-1,6-dihydro-1-pyrimidinyl]-N-[(1S)-1-[[5-(α,α-dimethylbenzyl)-1,3,4-oxadiazole-2-yl]carbonyl]-2-methylpropyl]acetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

40
[ 57625-74-8 ]
[ 251958-58-4 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

41
[ 57625-74-8 ]
2-[5-amino-6-oxo-2-phenyl-1,6-dihydro-1-pyrimidinyl]-N-[(1S)-1-[[5-(α,α-dimethylbenzyl)-1,3,4-oxadiazole-2-yl]carbonyl]-2-methylpropyl]acetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

42
[ 57625-74-8 ]
[ 1026751-56-3 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

43
[ 57625-74-8 ]
[ 1027923-09-6 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

44
[ 57625-74-8 ]
[ 337969-30-9 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

45
[ 57625-74-8 ]
[ 208840-36-2 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1268 - 1285

46
[ 57625-74-8 ]
[ 18755-52-7 ]

Reference： [1]Il Farmaco,1999,vol. 54,p. 600 - 610
[2]Journal of labelled compounds and radiopharmaceuticals,2011,vol. 54,p. 352 - 356

47
[ 57625-74-8 ]
[ 83799-24-0 ]