[ CAS No. 18962-07-7 ] {[proInfo.proName]}

Name: 18962-07-7|4-Isobutoxybenzaldehyde|95%
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Quality Control of [ 18962-07-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 18962-07-7 ]

SDS Specification

Alternatived Products of [ 18962-07-7 ]

Product Details of [ 18962-07-7 ]

CAS No. :	18962-07-7	MDL No. :	MFCD01922006
Formula :	C₁₁H₁₄O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PWASYRSZCSTUIW-UHFFFAOYSA-N
M.W :	178.23	Pubchem ID :	249810
Synonyms :

Calculated chemistry of [ 18962-07-7 ] Expand+

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.36
Num. rotatable bonds :	4
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	52.74
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) :	-5.19 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.37
Log Po/w (XLOGP3) :	3.09
Log Po/w (WLOGP) :	2.53
Log Po/w (MLOGP) :	2.03
Log Po/w (SILICOS-IT) :	2.86
Consensus Log Po/w :	2.58

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.97
Solubility :	0.191 mg/ml ; 0.00107 mol/l
Class :	Soluble
Log S (Ali) :	-3.31
Solubility :	0.0873 mg/ml ; 0.00049 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.31
Solubility :	0.0869 mg/ml ; 0.000488 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.19

Safety of [ 18962-07-7 ]

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

Application In Synthesis of [ 18962-07-7 ]

* 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 [ 18962-07-7 ]
Downstream synthetic route of [ 18962-07-7 ]

[ 18962-07-7 ] Synthesis Path-Upstream 1~6

1
[ 78-77-3 ]
[ 123-08-0 ]
[ 18962-07-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 70℃; for 3 h; Inert atmosphere	Step 2: Preparation of 4-isobutoxybenzaldehyde (Compound XIII) 4-Hydroxybenzaldehyde (10 g; 0.082 mol), potassium carbonate (33.95 g; 0.246 mol) and potassium iodide (1.36 g; 0.008 mol) were suspended in N,N-dimethylformamide (50 mL). Isobutyl bromide (26.7 mL; 0.246 mol) was added and the reaction was heated at 70° C. under nitrogen for 3 hours. The reaction was cooled down, diluted by using 150 mL of water and extracted by using 300 mL of ethyl acetate. The organic layer was extracted five times by using 150 mL of 10percent NaCl solution, dried under Na₂SO₄, filtered and concentrated which resulted in 14.3 g (98percent) of yellow oily product of 4-isobutoxybenzaldehyde (Compound XIII).
96%	With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 85℃; for 6 h;	In Three 250mL flask was added compound 7 (10.0g, 81.9mmol), anhydrous potassium carbonate (22.6g, 163.8 mmol), potassium iodide (1.4g, 8.2mmol) and 50mLDMF, heated to 85 deg C, bromine was slowly added to the reaction system on behalf of the isobutane (22.4g, 163.8mmol), the addition was completed, the reaction system for 3h at 85 deg C condition, and then continued to the system slowly added bromo-butane (11.2g, 81.9mmol), the system continues at 85 condition The reaction 3h.The reaction was stopped, cooled to room temperature, filtered and the filter cake was washed twice with 100mL of ethyl acetate.The filtrate was poured into 250mL of water, the organic phase was separated, the aqueous phase was extracted three times each with 100mL ethyl acetate and the combined organic phase was washed with 150mL saturated aqueous NaCl solution once, dried over anhydrous sodium sulfate, the drying is complete, filtered and the filtrate rotary done compound 8 14.0g, as a pale yellow liquid, yield 96percent
95%	With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 85℃; for 6 h;	Add p-hydroxybenzaldehyde (15.0g, 122.8mmo1) to anhydrous 250mL three-necked bottle, anhydrous potassium carbonate (25.4g,184.2mmoL),Potassium iodide (1.4 g, 12.3 mmoL) and 75 mL of DMF were heated to 85 ° C, and bromoisobutane (50.5 g, 368.4 mmol) was slowly added to the reaction system. After the addition, the system was reacted at 85 ° C for 6 h.The reaction was stopped, the system was cooled to room temperature, filtered, and the filter cake was washed twice with 90 mL of ethyl acetate.The filtrate was poured into 250 mL of water, the organic phase was separated, and the aqueous phase was extracted three times with 90 mL of ethyl acetate. The organic phase was combined and washed once with 150 mL of brine.Drying over anhydrous sodium sulfate, drying was completed, filtered, and the filtrate was dried to give 20.8 g of compound, pale yellow liquid, yield 95percent.

178 g

With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 100℃;

122g 4-hydroxybenzaldehyde (1mol), 600mL DMF, 256g of potassium carbonate (1.85 mol) of potassium iodide and 12g (0.07 mol) added to the reaction flask and heated to 100 deg.] C, dropwise addition of 274g bromo isobutane dropwise Bi, 100 deg.] C the reaction overnight, TLC show completion of the reaction of 4-hydroxybenzaldehyde to treatment, the reaction solution was filtered off with suction, washed with water and the filtrate washed with 600mL * 2 times 600mL dichloromethane, washed once with saturated brine 600mL, separated the organic phase was dried over anhydrous sodium sulfate, the solvent was evaporated to dryness to give 178 g product, directly into the next step.

Reference： [1] Patent: US2018/37549, 2018, A1, . Location in patent: Paragraph 0151
[2] Patent: CN105418460, 2016, A, . Location in patent: Paragraph 0053; 0056; 0057; 0058; 0059
[3] Patent: CN108358817, 2018, A, . Location in patent: Paragraph 0055; 0056; 0057
[4] Russian Journal of General Chemistry, 2005, vol. 75, # 7, p. 1113 - 1124
[5] Patent: WO2006/36874, 2006, A1, . Location in patent: Page/Page column 21
[6] Chemical and Pharmaceutical Bulletin, 2010, vol. 58, # 5, p. 752 - 754
[7] Patent: WO2014/85362, 2014, A1, . Location in patent: Paragraph 0066
[8] Chemical Communications, 2015, vol. 51, # 16, p. 3403 - 3406
[9] Patent: WO2017/15272, 2017, A1, . Location in patent: Paragraph 0203
[10] Patent: CN107011137, 2017, A, . Location in patent: Paragraph 0016; 0028; 0029
[11] Patent: CN107216271, 2017, A, . Location in patent: Paragraph 0054; 0055

2
[ 513-38-2 ]
[ 123-08-0 ]
[ 18962-07-7 ]

Reference： [1] Patent: US2699448, 1952, ,
[2] Patent: WO2008/112368, 2008, A2, . Location in patent: Page/Page column 37-38

3
[ 78-83-1 ]
[ 459-57-4 ]
[ 18962-07-7 ]

Yield	Reaction Conditions	Operation in experiment
0.6 g	With tetra(n-butyl)ammonium hydrogensulfate; potassium hydroxide In water; toluene at 50 - 52℃;	Example 2g: Alternatively 4-zso-butyloxybenzylamine (SM2) and 4-iso- but loxybenzylamine acetate (SM2b) are prepared according to following scheme. [0214] KOH (1.36g, 24.2 mmol, 3 eq) was dissolved in water (1.4 ml) and added to the solution of 4-fluorobenzaldehyde (1.0 g, 8.1 mmol, 1 eq). Isobutanol (0.66 g, 8.9 mmol, 1.1 eq) and tetrabutyl ammonium hydrogensulfate (TBAH, 0.27 g) in toluene (7 ml). The reaction mixture was vigorously stirred at 50-52 °C overnight and thereafter diluted with water (5 ml), dried and concentrated in vacuo to give 0.877 g of crude product. The crude product was purified by column chromatography using ethyl acetate : heptane to give 0.6 g of 4-isobutoxy benzaldehyde. 4-Isobutoxy benzaldehyde can thereafter be converted to SM2 and SM2b respectively using the procedure outline in example 2b.

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 10, p. 2547 - 2550
[2] Patent: WO2017/15272, 2017, A1, . Location in patent: Paragraph 0214

4
[ 513-38-2 ]
[ 497-19-8 ]
[ 123-08-0 ]
[ 18962-07-7 ]

Yield	Reaction Conditions	Operation in experiment
0.125 mol, 46%	With potassium hydroxide In ethanol	(a) Synthesis of 4-(2-methylpropoxy)benzaldehyde A 1000 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-hydroxybenzaldehyde (33.18 g, 0.272 mol), 100 ml of ethanol, and a solution of potassium hydroxide (20.42 g, 0.309 mol) in 100 mL of ethanol. The reaction mixture is heated with stirring for one-half hour. Next 1-iodo-2-methylpropane (100 g, 0.543 mol) is added and the mixture refluxed for 12 hours. After cooling, the solvents are removed by rotary evaporation to yield a brown solid which is added to a separatory funnel containing 500 mL ether and 500 mL of 5percent aqueous sodium carbonate. The layers are separated and the aqueous phase is washed with ether (2500 mL). The combined ether layers are washed with pH 12 sodium hydroxide solution (5200 mL) until the washes are colorless. The organic solution is then washed with brine (100 mL) and dried over magnesium sulfate. After filtration and removal of the solvents by rotary evaporation, a viscous yellow liquid is obtained. This material is purified by Kugel-Rohr distillation to give 22.3 g (0.125 mol, 46percent) of a colorless liquid. ¹ H NMR (60 MHz, CDCl₃): 1.00 (d, 6H); 2.0 (m, 1H); 3.65 (d, 2H); 6.75, 6.90, 7.60, 7.75 (aa'bb' quartet, 4H); 9.75 (s, 1H).

Reference： [1] Patent: US4999186, 1991, A,

5
[ 1126-75-6 ]
[ 18962-07-7 ]

Reference： [1] Journal fuer Praktische Chemie (Leipzig), 1956, vol. <4> 3, p. 274,275

6
[ 100-97-0 ]
[ 40141-14-8 ]
[ 18962-07-7 ]

Reference： [1] Journal fuer Praktische Chemie (Leipzig), 1956, vol. <4> 3, p. 274,275

[ 18962-07-7 ] Synthesis Path-Downstream 1~87

1
[ 54-85-3 ]
[ 18962-07-7 ]
isonicotinic acid-(4-isobutoxy-benzylidenehydrazide) [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1953,vol. 75,p. 1933,1934

2
[ 100-97-0 ]
[ 40141-14-8 ]
[ 18962-07-7 ]

Reference： [1]Journal fur praktische Chemie (Leipzig 1954),1956,vol. <4> 3,p. 274,275

3
[ 513-38-2 ]
[ 123-08-0 ]
[ 18962-07-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; In N,N-dimethyl-formamide; at 50℃; for 100h;	A 75 mL mini-block tube equipped with a magnetic stirrer bar was charged with 6.16 g (50.4 mmol) of 4-hydroxybenzaldehyde, 4.40 mL (8.58 g, 55.0 mmol) of isobutyl iodide 30 mL of dimethylformamide and 6.05 g (57.1 mmol) of sodium carbonate. The slurry was heated to 500C.After 40 hours the reaction was only 50% complete so another 3 ml (5.85 g, 37.4 mmol) isobutyl iodide was added. After 60 more hours another 3 mL (5.85 g, 37.4 mmol) isobutyl iodide and 3 g (28.5 mmol) of sodium carbonate were added. The reaction mixture was cooled to 25C and diluted with methyl t-butyl ether (MTBE) and water. The organic layer was decanted off. The aqueous phase was rinsed with MTBE, again decanting off the organic layer. The combined organic layers were washed with 2N aqueous sodium hydroxide (3 X 30 mL) and brine (1 X 30 mL), dried over sodium sulfate and concentrated to give 4-Isobutoxybenzaldehyde which was used as (following the above procedure for 3-(4-t-butylphenyl)propanoic acid (Example 6) to prepare 3-(4- <n="39"/>Isobutoxyphenyl)propanoic acid (1.31 g) as an off-white solid. IH NMR (d6-DMS0): δ 12.0, bs, IH (COOH); δ 7.00, d, 2H, (arylH's meta to O); δ 6.70, d, 2H (arylH's ortho to O); δ 3.60, d, 2H, (OCH2); 2.65, t, 2H, (CH2 α to aryl); δ 2.38, t, 2H (CH2 α to COOH); δ 1.89, n, IH, (CH); δ 0.87, d, 6H (CH3's). 13C NMR (d6-DMS0): 173.76, 157.06, 132.61, 129.12, 114.26, 73.67, 35.56, 29.47, 27.68, 19.04.

Reference： [1]Patent: US2699448,1952,A
[2]Patent: WO2008/112368,2008,A2 .Location in patent: Page/Page column 37-38

4
[ 18962-07-7 ]
[ 131-22-6 ]
[ 20715-59-7 ]

Reference： [1]Diss.<Leipzig 1939> S.49,

5
[ 18962-07-7 ]
[ 21198-80-1 ]
[ 109097-70-3 ]

Reference： [1]Patent: BE544031,1959,A
Chem.Abstr.,1960,vol. 54
Chem.Abstr.,1960,vol. 54

6
[ 288-16-4 ]
[ 18962-07-7 ]
[ 90672-89-2 ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1245 - 1253

7
[ 6704-35-4 ]
[ 18962-07-7 ]
(E)-4-(4-Isobutoxy-phenyl)-1-morpholin-4-yl-but-3-en-2-one [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,1985,vol. 20,p. 495 - 500

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; sodium iodide; In N,N-dimethyl-formamide; at 80℃;	General procedure: A suspension of 4-hydroxybenzaldehyde (200 mg, 1.64 mmol), l-chloro-3,3- dimethylbutane (395 mg, 1.97 mmol), sodium iodide (24 mg, 0.16 mmol), and cesium carbonate (800 mg, 2.46 mmol) in anhydrous dimethylformamide (5 raL) was stirred at 80 C overnight. After cooling to room temperature, solids were filtered and washed with ether. The filtrate was washed with 2 N sodium hydroxide (2 20 mL), water (20 mL), and brine (20 mL), dried over magnesium sulfate, filtered, and concentrated to give 4-(3,3- dimethylbutoxy)benzaldehyde (262 mg, 78% crude) as a pale yellow oil that was used without further purification or characterization.
	With potassium carbonate; In acetone; at 65℃;	General procedure: In a round bottom flask,1 mmol of p-hydroxybenzaldehyde was added,20mL acetone dissolved,Stir evenly,3.0 mmol of potassium carbonate was added,A mixture of 1.0 equiv haloalkanes (bromomethylcyclopropane,1-bromo-3-methyl-2-butene,Bromo isobutane) in acetone solution 5 mL,The reaction was then allowed to reflux at an oil bath temperature of 65 C,The time and temperature of the reaction can be adjusted according to TLC detection,In order to carry out the reaction more thoroughly,Can be added in the middle of the reaction of 0.5equiv potassium carbonate,After the end of the reaction,First, the reaction solution was filtered under reduced pressure,The acetone solvent in the filtrate was distilled off under reduced pressure,The resulting mixture was then dissolved in methanol,Can be dissolved,Add 10 mL of the appropriate amount of saturated aqueous solution of potassium carbonate,Stirred at room temperature for 30 min,By potassium carbonate and unreacted 4-hydroxy acid esterification reaction,And then extracted with methylene chloride and saturated aqueous sodium chloride into the aqueous phase,According to the organic phase color to determine the number of extraction,Usually 3 times for the best,It is possible to remove the reaction substrate which does not participate in the reaction,The organic phase was dried with anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain an etherified product having a high purity.

9
[ 2295-31-0 ]
[ 18962-07-7 ]
5-[1-(4-Isobutoxy-phenyl)-meth-(Z)-ylidene]-thiazolidine-2,4-dione [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2547 - 2550

10
[ 78-83-1 ]
[ 459-57-4 ]
[ 18962-07-7 ]

Yield	Reaction Conditions	Operation in experiment
0.6 g	With tetra(n-butyl)ammonium hydrogensulfate; potassium hydroxide; In water; toluene; at 50 - 52℃;	Example 2g: Alternatively 4-zso-butyloxybenzylamine (SM2) and 4-iso- but loxybenzylamine acetate (SM2b) are prepared according to following scheme. [0214] KOH (1.36g, 24.2 mmol, 3 eq) was dissolved in water (1.4 ml) and added to the solution of 4-fluorobenzaldehyde (1.0 g, 8.1 mmol, 1 eq). Isobutanol (0.66 g, 8.9 mmol, 1.1 eq) and tetrabutyl ammonium hydrogensulfate (TBAH, 0.27 g) in toluene (7 ml). The reaction mixture was vigorously stirred at 50-52 C overnight and thereafter diluted with water (5 ml), dried and concentrated in vacuo to give 0.877 g of crude product. The crude product was purified by column chromatography using ethyl acetate : heptane to give 0.6 g of 4-isobutoxy benzaldehyde. 4-Isobutoxy benzaldehyde can thereafter be converted to SM2 and SM2b respectively using the procedure outline in example 2b.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2547 - 2550
[2]Patent: WO2017/15272,2017,A1 .Location in patent: Paragraph 0214

11
[ 78-77-3 ]
[ 123-08-0 ]
[ 18962-07-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 70℃; for 3h;Inert atmosphere;	Step 2: Preparation of 4-isobutoxybenzaldehyde (Compound XIII) 4-Hydroxybenzaldehyde (10 g; 0.082 mol), potassium carbonate (33.95 g; 0.246 mol) and potassium iodide (1.36 g; 0.008 mol) were suspended in N,N-dimethylformamide (50 mL). Isobutyl bromide (26.7 mL; 0.246 mol) was added and the reaction was heated at 70 C. under nitrogen for 3 hours. The reaction was cooled down, diluted by using 150 mL of water and extracted by using 300 mL of ethyl acetate. The organic layer was extracted five times by using 150 mL of 10% NaCl solution, dried under Na2SO4, filtered and concentrated which resulted in 14.3 g (98%) of yellow oily product of 4-isobutoxybenzaldehyde (Compound XIII).
96%	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 85℃; for 6h;	In Three 250mL flask was added compound 7 (10.0g, 81.9mmol), anhydrous potassium carbonate (22.6g, 163.8 mmol), potassium iodide (1.4g, 8.2mmol) and 50mLDMF, heated to 85 deg C, bromine was slowly added to the reaction system on behalf of the isobutane (22.4g, 163.8mmol), the addition was completed, the reaction system for 3h at 85 deg C condition, and then continued to the system slowly added bromo-butane (11.2g, 81.9mmol), the system continues at 85 condition The reaction 3h.The reaction was stopped, cooled to room temperature, filtered and the filter cake was washed twice with 100mL of ethyl acetate.The filtrate was poured into 250mL of water, the organic phase was separated, the aqueous phase was extracted three times each with 100mL ethyl acetate and the combined organic phase was washed with 150mL saturated aqueous NaCl solution once, dried over anhydrous sodium sulfate, the drying is complete, filtered and the filtrate rotary done compound 8 14.0g, as a pale yellow liquid, yield 96%
95%	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 85℃; for 6h;	Add p-hydroxybenzaldehyde (15.0g, 122.8mmo1) to anhydrous 250mL three-necked bottle, anhydrous potassium carbonate (25.4g,184.2mmoL),Potassium iodide (1.4 g, 12.3 mmoL) and 75 mL of DMF were heated to 85 C, and bromoisobutane (50.5 g, 368.4 mmol) was slowly added to the reaction system. After the addition, the system was reacted at 85 C for 6 h.The reaction was stopped, the system was cooled to room temperature, filtered, and the filter cake was washed twice with 90 mL of ethyl acetate.The filtrate was poured into 250 mL of water, the organic phase was separated, and the aqueous phase was extracted three times with 90 mL of ethyl acetate. The organic phase was combined and washed once with 150 mL of brine.Drying over anhydrous sodium sulfate, drying was completed, filtered, and the filtrate was dried to give 20.8 g of compound, pale yellow liquid, yield 95%.

68.7%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 24h;	Step I: Weigh 4-hydroxybenzaldehyde Weigh p-hydroxybenzaldehyde (12.2g, 100mmol), bromoisobutane (13.7g, 100mmol), K2CO3 (69g, 500mmol) in a 250ml flask, add 100mL DMF , Stir the reaction at 80 degrees for 24h. Stop the reaction, pour the reaction solution into 800 mL of water, stir until K2C03 is dissolved, and extract 3 times with EA. Combine the organic phases and wash with 2mol/L NaOH solution, water, and saturated brine successively, dry with anhydrous sodium sulfate, and distill off the solvent. , Obtain 12.23g of pale yellow liquid p-isobutoxybenzaldehyde with a yield of 68.7%.
	With potassium carbonate; In ethanol; at 74 - 78℃; for 120h;Heating / reflux;	b) Preparation of [0103] 4-Hydroxybenzaldehyde (4.0 kg) and ethanol (20 1) were added to a solution of isobutyl bromide (9.0 kg) in ethanol (15 1). Potassium carbonate (13.6 kg) was added and the suspension was refluxed (74-78 0C) for 5 days. The residual 4- hydroxybenzaldehyde was checked by HPLC (< 10%). The suspension was cooled to 20 0C and used in the next step.
	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at -10 - 82℃; for 6.83h;Large scale;	b) Preparation of[00661 The reaction step was performed in two batches. 4-Hydroxybenzaldehyde (141 kg) was dissolved in dimethylformamide (335 kg) at 15-25C, then solid potassium carbonate (323 kg) and potassium iodide (19 kg) were added portion wise at <30C and the suspension was heated up to 78-82C. The temperature of the condenser was fixed to -10C and isobutylbromide (317 kg) was added to the suspension over 4 h 50 mm at 78-82C. At the end of the addition, the mixture was stirred for 2 h at 78-82C and residual starting material was checked by HPLC. The suspension was cooled to 20-30C, diluted with 100% ethanol (501 kg, denatured with isopropanol), stirred for 15 mm at 20-30C and centrifuged (3 loadings) to remove the excess of carbonate and potassium bromide. The line and the cake were washed with 100% ethanol (2 x 32 kg/loading). The solution is used as such in the next step.
	With potassium carbonate; In ethanol; at 74 - 78℃; for 120h;Reflux; Large scale;	4-Hydroxybenzaldehyde (4.0 kg) and ethanol (20 L) were added to a solution of isobutyl bromide (9.0 - 10 kg) in ethanol (15-18 L). Potassium carbonate (13-14 kg) was added and the suspension was refluxed (74-78 C) for 5 days. The residual 4-hydroxybenzaldehyde was checked by HPLC (< 10%). The suspension was cooled to 20 C and used in the next step.
178 g	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 100℃;	122g 4-hydroxybenzaldehyde (1mol), 600mL DMF, 256g of potassium carbonate (1.85 mol) of potassium iodide and 12g (0.07 mol) added to the reaction flask and heated to 100 deg.] C, dropwise addition of 274g bromo isobutane dropwise Bi, 100 deg.] C the reaction overnight, TLC show completion of the reaction of 4-hydroxybenzaldehyde to treatment, the reaction solution was filtered off with suction, washed with water and the filtrate washed with 600mL * 2 times 600mL dichloromethane, washed once with saturated brine 600mL, separated the organic phase was dried over anhydrous sodium sulfate, the solvent was evaporated to dryness to give 178 g product, directly into the next step.
		50.0 g (0.41 mol) of p-hydroxybenzaldehyde, 84.8 g (0.62 mol) of potassium carbonate, 2.0 g(0.012 mol) of potassium iodide were added to 200 ml of N, N-dimethylformamide, stirred at room temperature for 10 min,111.4 g (0.82 mol) of bromoisobutane,The reaction was heated to 83 C for 24h. The reaction was completed, suction filtration, the filtrate was poured into 300ml mass fraction of 4% aqueous sodium hydroxide solution for 5min, 350 × 2 ethyl acetate extraction 2 times, the combined organic layer was washed with 500ml × 2 saturated brine, dried over anhydrous sodium sulfate ,The solvent was distilled off under reduced pressure to give 64.6 g of crude 4-isobutoxybenzaldehyde as a pale yellow oil, yield: 88.5%
	With potassium carbonate; In N,N-dimethyl-formamide; at 30 - 82℃; for 7h;	14.1 g (115.5 mmol) of p-hydroxybenzaldehyde was dissolved in DMF.Add anhydrous potassium carbonate 32.3g (233.7mmol),maintain the temperature below 30C,31.7 g (231.4 mmol) of isobutyl bromide was slowly added to the suspension.The reaction was carried out at 78-82C for 7 h, and the progress of the reaction was monitored by HPLC.The reaction is completed. The temperature was lowered to 20-30C, 50 g of absolute ethanol was added and stirred for 15 min, and suction-filtered, and washed with 10 g of absolute ethanol twice. The organic phases were combined and the next step was carried out directly.

Reference： [1]Patent: US2018/37549,2018,A1 .Location in patent: Paragraph 0151
[2]Patent: CN105418460,2016,A .Location in patent: Paragraph 0053; 0056; 0057; 0058; 0059
[3]Patent: CN108358817,2018,A .Location in patent: Paragraph 0055; 0056; 0057
[4]Patent: CN113274390,2021,A .Location in patent: Paragraph 0021; 0022
[5]Russian Journal of General Chemistry,2005,vol. 75,p. 1113 - 1124
[6]Patent: WO2006/36874,2006,A1 .Location in patent: Page/Page column 21
[7]Chemical and Pharmaceutical Bulletin,2010,vol. 58,p. 752 - 754
[8]Patent: WO2014/85362,2014,A1 .Location in patent: Paragraph 0066
[9]Chemical Communications,2015,vol. 51,p. 3403 - 3406
[10]Patent: WO2017/15272,2017,A1 .Location in patent: Paragraph 0203
[11]Patent: CN107011137,2017,A .Location in patent: Paragraph 0016; 0028; 0029
[12]Patent: CN107216271,2017,A .Location in patent: Paragraph 0054; 0055
[13]Patent: CN109734652,2019,A .Location in patent: Paragraph 0027; 0035; 0036

12
[ 141-82-2 ]
[ 18962-07-7 ]
3-amino-3-(4-isobutoxy-phenyl)-propionic acid [ No CAS ]
[ 119103-97-8 ]

Reference： [1]Russian Journal of General Chemistry,2005,vol. 75,p. 1113 - 1124

13
[ 871100-06-0 ]
[ 18962-07-7 ]
C₂₉H₃₃N₃O₄ [ No CAS ]

Reference： [1]Molecular Pharmacology,2007,vol. 72,p. 976 - 983

14
[ 18962-07-7 ]
[ 85002-23-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2547 - 2550

15
[ 18962-07-7 ]
5-[Chloro-(4-isobutoxy-phenyl)-methyl]-isothiazole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1245 - 1253

16
[ 18962-07-7 ]
1-[(4-Isobutoxy-phenyl)-isothiazol-5-yl-methyl]-4-methyl-piperazine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1245 - 1253

17
[ 18962-07-7 ]
[ 101455-10-1 ]

Reference： [1]European Journal of Medicinal Chemistry,1985,vol. 20,p. 495 - 500

18
[ 1126-75-6 ]
[ 18962-07-7 ]

Reference： [1]Journal fur praktische Chemie (Leipzig 1954),1956,vol. <4> 3,p. 274,275

19
[ 18962-07-7 ]
4-isobutoxybenzaldehyde oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With hydroxylamine; In ethanol; water; at 77℃; for 3h;Heating / reflux;	c) Preparation of [O104] Hydroxylamine (50% in water, 8.7 kg) was added to the product from previous step b)(174 1, 176 kg) and ethanol (54 1). The suspension was refluxed (77 0C) for 3 h. Unreacted residual amounts of the compound of step b was checked by HPLC (< 5%). The suspension was cooled to 30 0C, filtered and the filter was washed with ethanol (54 1). The solution was concentrated by distillation under reduced pressure at 30 0C to a residual volume of 67 litters. The solution was cooled to 25 0C and water (110 1) was added. The suspension was concentrated by distillation under reduced pressure at 30 0C to a residual volume of 102 litters. Petrol ether (60-90 fraction, 96 1) was added and the mixture was heated to reflux (70 0C). The solution Λvas cooled to 40 0C and crystallization was initiated by seeding. The suspension was cooled to 5 0C and stirred for 4h. The product was centrifuged and the cake was washed with petrol ether (60-90 fraction, 32 1). The wet cake was dried at about 40 0C to yield 16kg product (63%).

Reference： [1]Patent: WO2006/36874,2006,A1 .Location in patent: Page/Page column 21

20
[ 38870-89-2 ]
[ 18962-07-7 ]
[ 865137-99-1 ]

Yield	Reaction Conditions	Operation in experiment
60%	With aluminum (III) chloride; In nitromethane; at 0℃; for 3h;	To a mixture of <strong>[18962-07-7]4-isobutoxybenzaldehyde</strong> (6.9 g, 38.7 mmol), aluminum chloride (12.9 g, 96.8 mmol) and nitromethane (39 mL) was added methoxyacetyl chloride (4.1 mL, 44.5 mmol), with stirring at 0C, and the mixture was stirred at the same temperature for 3 hr. After completion of the reaction, the reaction mixture was poured into ice water, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=4/1) to give the title compound (5.22 g, yield 60%) as colorless crystals. 1H NMR (CDCl3) δ: 1.08(6H, d, J=6.9Hz), 2.19(1H, m), 3.89(2H, d, J=6.0Hz), 4.68(2H, s), 6.98(1H, d, J=8.4Hz), 7.84(1H, dd, J=2.1, 8.4Hz), 7.91(1H, d, J=2.1Hz), 9.89(1H, s).
60%		To a mixture of <strong>[18962-07-7]4-isobutoxybenzaldehyde</strong> (6.9 g, 38.7 mmol), aluminum chloride (12.9 g, 96.8 mmol) and nitromethane (39 mL) was added methoxyacetyl chloride (4.1 mL, 44.5 mmol) under stirring at 0C, and the mixture was stirred at the same temperature for 3 hr. After completion of the reaction, the reaction mixture was poured into ice water, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-4/1) to give the title compound (5.22 g, yield 60%) as colorless crystals. 1H NMR (CDCl3) δ: 1.08(6H, d, J=6.9Hz), 2.19(1H, m), 3. 89 (2H, d, J=6.0Hz), 4.68(2H, s), 6.9.8(1H, d, J=8.4Hz), 7.84(1H, dd, J=8.4, 2.1Hz), 7.91(1H, d, J=2.1Hz), 9.89(1H s).

Reference： [1]Patent: EP1731505,2006,A1 .Location in patent: Page/Page column 36-37
[2]Patent: EP1726580,2006,A1 .Location in patent: Page/Page column 55-56

21
[ 513-38-2 ]
[ 497-19-8 ]
[ 123-08-0 ]
[ 18962-07-7 ]

Yield	Reaction Conditions	Operation in experiment
22.3 g (0.125 mol, 46%)	With potassium hydroxide; In ethanol;	(a) Synthesis of 4-(2-methylpropoxy)benzaldehyde A 1000 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-hydroxybenzaldehyde (33.18 g, 0.272 mol), 100 ml of ethanol, and a solution of potassium hydroxide (20.42 g, 0.309 mol) in 100 mL of ethanol. The reaction mixture is heated with stirring for one-half hour. Next 1-iodo-2-methylpropane (100 g, 0.543 mol) is added and the mixture refluxed for 12 hours. After cooling, the solvents are removed by rotary evaporation to yield a brown solid which is added to a separatory funnel containing 500 mL ether and 500 mL of 5% aqueous sodium carbonate. The layers are separated and the aqueous phase is washed with ether (2500 mL). The combined ether layers are washed with pH 12 sodium hydroxide solution (5200 mL) until the washes are colorless. The organic solution is then washed with brine (100 mL) and dried over magnesium sulfate. After filtration and removal of the solvents by rotary evaporation, a viscous yellow liquid is obtained. This material is purified by Kugel-Rohr distillation to give 22.3 g (0.125 mol, 46%) of a colorless liquid. 1 H NMR (60 MHz, CDCl3): 1.00 (d, 6H); 2.0 (m, 1H); 3.65 (d, 2H); 6.75, 6.90, 7.60, 7.75 (aa'bb' quartet, 4H); 9.75 (s, 1H).

Reference： [1]Patent: US4999186,1991,A

22
[ 18962-07-7 ]
[ 119103-97-8 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; sodium hydroxide; malonic acid;	(b) Synthesis of 4-(2-methylpropoxy)cinnamic acid A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-(2-methylpropoxy)benzaldehyde (17.84 g, 0.100 mol, as from Example 2a), malonic acid (10.42 g, 0.100 mol), and 19 mL of pyridine. The mixture is heated with stirring in a 130 C. oil bath for 24 hours, then stirred at room temperature for 16 hours. The reaction mixture is then poured into a separatory funnel containing 300 mL of pH 12 aqueous sodium hydroxide and 300 mL of ether. The layers are separated and the aqueous phase washed with 150 mL of ether. The aqueous phase is then acidified with concentrated hydrochloric acid to bring the pH to 1 whereupon the powdery white acid precipitates out. The mixture is chilled in an ice/salt bath and the solid collected giving 5.89 g (0.027 mol, 27%) of product, m.p. 161-164 C. 1 H NMR (60 MHz, CDCl3): 1.05 (d, 6H); 2.0 (m, 1H); 3.75 (d, 2H); 6.3 (d, 1H, J=16 Hz); 6.8, 6.95, 7.3, 7.45 (aa'bb' quartet, 4H); 7.7 (d, 1H, J=16 Hz); 10.9 (br s, 1H).

Reference： [1]Patent: US4999186,1991,A

23
[ 79-19-6 ]
[ 18962-07-7 ]
[ 20718-94-9 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2010,vol. 58,p. 752 - 754

24
[ 610-99-1 ]
[ 18962-07-7 ]
3-hydroxy-1-(2-hydroxyphenyl)-3-(4-isobutoxyphenyl)-2-methylpropan-1-one [ No CAS ]
3-hydroxy-1-(2-hydroxyphenyl)-3-(4-isobutoxyphenyl)-2-methylpropan-1-one [ No CAS ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 2676 - 2688

25
[ 896464-16-7 ]
[ 18962-07-7 ]
[ 1394898-79-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4281 - 4287

26
[ 18962-07-7 ]
[ 1383719-93-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4281 - 4287

27
[ 18962-07-7 ]
[ 1383719-94-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4281 - 4287

28
[ 18962-07-7 ]
[ 1383720-12-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4281 - 4287

29
[ 18962-07-7 ]
[ 706779-91-1 ]

Reference： [1]Patent: WO2014/85362,2014,A1
[2]Patent: CN105418460,2016,A
[3]Patent: CN105418460,2016,A
[4]Patent: CN105418460,2016,A
[5]Patent: CN105418460,2016,A
[6]Patent: CN105418460,2016,A
[7]Patent: WO2017/15272,2017,A1
[8]Patent: WO2017/15272,2017,A1
[9]Patent: WO2017/15272,2017,A1
[10]Patent: WO2017/15272,2017,A1
[11]Patent: WO2017/15272,2017,A1
[12]Patent: WO2017/15272,2017,A1
[13]Patent: WO2017/15272,2017,A1
[14]Patent: WO2017/15272,2017,A1
[15]Patent: WO2017/15272,2017,A1
[16]Patent: WO2017/15272,2017,A1
[17]Patent: WO2017/15272,2017,A1
[18]Patent: WO2017/15272,2017,A1
[19]Patent: WO2017/15272,2017,A1
[20]Patent: WO2017/15272,2017,A1
[21]Patent: WO2017/15272,2017,A1
[22]Patent: WO2017/15272,2017,A1
[23]Patent: WO2017/15272,2017,A1
[24]Patent: WO2017/15272,2017,A1
[25]Patent: WO2017/15272,2017,A1
[26]Patent: WO2017/15272,2017,A1
[27]Patent: WO2017/15272,2017,A1
[28]Patent: WO2017/15272,2017,A1
[29]Patent: WO2017/15272,2017,A1
[30]Patent: WO2017/15272,2017,A1
[31]Patent: CN106588753,2017,A
[32]Patent: CN107200707,2017,A
[33]Patent: US2018/37549,2018,A1
[34]Patent: US2018/37549,2018,A1
[35]Patent: US2018/37549,2018,A1
[36]Patent: US2018/37549,2018,A1
[37]Patent: US2018/37549,2018,A1
[38]Patent: CN108358817,2018,A
[39]Patent: CN108358817,2018,A
[40]Patent: WO2017/36432,2017,A1
[41]Patent: WO2017/36432,2017,A1
[42]Patent: CN113274390,2021,A

30
[ 18962-07-7 ]
[ 882035-15-6 ]

Yield	Reaction Conditions	Operation in experiment
96.8%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 20 - 25℃; for 1h;Large scale;	Take a 20 L reaction flask, add 1.00 kg (5.61 mol) of <strong>[18962-07-7]4-isobutoxybenzaldehyde</strong> (formula V) and 10 L of ethanol,1.5 L (11.25 mol) of a 30% aqueous solution of sodium hydroxide was added with stirring,The final fraction was added 0.47 kg (6.76 mol) of hydroxylamine hydrochloride,After the addition reaction was 25 deg.] C was stirred at room temperature for one hour.50 C under reduced pressure to remove ethanol,Concentrates precipitate a large amount of solids,Add 10 L of water, stir well for 1 hour,The filter cake was washed with 2 L of water.The solid was dried under reduced pressure at 70 C for 24 hours,To give 1.05 kg of product (yield: 96.8%).
95%	With hydroxylamine hydrochloride; sodium hydroxide; In water; at 20℃; for 0.916667h;	Hydroxylamine hydrochloride (15.6 g, 0.224 mol) and sodium hydroxide (8.98 g, 0.224 mol) were added to 100 g of water at room temperature and stirred for 15 minutes. A solution of <strong>[18962-07-7]4-isobutoxybenzaldehyde</strong> (20 g, 0.112 mol), reacted at room temperature for 40 min, After the reaction was completed, the ethanol was distilled off under reduced pressure and extracted with water (250 mL) and dichloromethane (250 mL). The organic layer was separated and the aqueous layer was washed with dichloromethane (100 mL * 2). The organic phases were combined and saturated The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and the methylene chloride was evaporated under reduced pressure. The crude <strong>[18962-07-7]4-isobutoxybenzaldehyde</strong> oxime was obtained. The crude product was recrystallized, add petroleum ether (25.0g), heated to reflux, the crude product was dissolved, maintained for 1 hour. After stirring at 0-5 C for 5 hours, the solid precipitated and was filtered to obtain 20.60 g of the product in a yield of 95%.
95.96%	With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol; water; at 20℃; for 3h;	Step II: Weigh sodium bicarbonate (4.62g, 55mmol) and hydroxylamine hydrochloride (3.82g, 55mmol) into a flask, add 30ml of water, stir and react at room temperature for 20min to obtain hydroxylamine aqueous solution. Weigh p-isobutoxybenzaldehyde (8.91 g, 50 mmol) and place it in a flask, add 50 mL of EtOH and stir to dissolve, add the aqueous hydroxylamine solution to the flask while stirring, and react at room temperature for 3 hours. Ethanol was evaporated under reduced pressure, and a white solid was precipitated. The filter cake was filtered with suction and washed with water. After drying, 9.62 g of p-isobutoxybenzaldehyde oxime was obtained as a white solid with a yield of 95.96%.

75%	With hydroxylamine hydrochloride; potassium carbonate; In ethanol; water; for 2h;Reflux;	In 500mL single jar added Compound 8 (10.0g, 56.1mmol), 250mL ethanol, K2CO3(38.7g, 280.5mmol); hydroxylamine hydrochloride (19.5g, 280.5mmol) was dissolved in 15mL water, and then added to the system, the addition was completed, the system heated at reflux for 2h, the reaction was stopped, cooled to room temperature, the system was filtered, the filtrate was rotary evaporated to 100mL, 250mL and poured into water, and extracted three times with 100mL ethyl acetate.The combined organic phase was washed with 150mL saturated aqueous NaCl solution once, dried over anhydrous sodium sulfate, the drying is complete, filtered and the filtrate concentrated to give the crude product was purified using column chromatography (developing solvent polarity: petroleum ether / ethyl acetate = 20/1) 9 obtained as a white solid, a yield of 75% 8.1g compound
196 kg	With hydroxylamine; In ethanol; water; at 20 - 77℃; for 2.5h;Large scale;	c) Preparation of[0067j To the aldehyde solution resulting from Step b, 50% hydroxylamine in water (115 kg) was added at room temperature over 0.5 h (the addition is slightly exothermic), the line washed with ethanol (8 kg), then the bulk was heated up to 73-77C and stirred at this temperature for 2h. The bulk was concentrated under reduced pressure (250-120 mbar, 45-55C) to 850 L, the residue quenched with water (951 kg) at 45-55C and the residual ethanol distilled under vacuum (270-150 mbar, 45-55C, residual volume = 1466 L). The bulk was diluted with petrol ether 60- 90 (557 kg) and heated at reflux (60C) to reach complete dissolution (20 mm, visual check). The solution was cooled down to 8-12C (crystallization occurs at T = 27C) over 5.5 h. AfterQH 0.5 h stirring at 10C, the mixture was cooled to 0-5C and stirred at this temperature for 2 h. The bulk was centrifuged (3 loadings) and the cake washed with petrol ether (2 x 23 kg/loading), then dried under reduced pressure at 40C to afford the crude oxime (212 kg).Recrystallization:[00681 The crude product (212 kg) was dissolved in hexane (642 kg) at 15-25C and the suspension heated up to 62C. Charcoal (6 kg) in hexane (26 kg) was added and the suspension was stirred for 0.5 h. After filtration (the filter was washed with 33 kg hexane), the solution was cooled to crystallisation temperature (55C), and the mixture was stirred for 1 h at this temperature. The suspension was cooled to 10-15C. After stirring for 2 h at that temperature, the bulk was centrifuged (3 loadings) and the cake washed with cold hexane (2 x 13 kg/loading), then dried under reduced pressure at 40C.[0069j Yield oxime: 196 kg (87.9% over the two steps)
	With hydroxylamine; In ethanol; at 77℃;Reflux; Large scale;	Preparation of [0204] Hydroxylamine (50% in water, 8-9 kg) was added to the aldehyde (<strong>[18962-07-7]4-isobutoxybenzaldehyde</strong>) obtained in the previous step (174 L, 176 kg) and ethanol (54 L). The suspension was refluxed (77 C) for 3-5 h. Unreacted residual aldehyde was checked by HPLC (< 5%). The suspension was cooled to 30 C, filtered and the filter was washed with ethanol (54 L). The solution was concentrated by distillation under reduced pressure at 30 C to a residual volume of 65 - 70 liters. The solution was cooled to 25 C and water (1 10 L) was added. The suspension was concentrated by distillation under reduced pressure at 30 C to a residual volume of 100-105 liters. Petroleum ether (60-90 fraction, 90-100 L) was added and the mixture was heated to reflux (70-80 C). The solution was cooled to 40 C and crystallization was initiated by seeding. The suspension was cooled to 0-5 C and stirred for 3-6h. The product was centrifuged and the cake was washed with petroleum ether (60-90 fraction, 32 L). The wet cake was dried at about 40 C to yield 15- 18kg product (60-70%) used in the next step.
21.2 g	With hydroxylamine hydrochloride; sodium hydroxide; In water; at 73 - 77℃; for 2h;	6.0 g (181.6 mmol) of hydroxylamine hydrochloride was added to the above ethanol solution, and then 17 g of a 20% sodium hydroxide solution was slowly added.After heating, it was heated to 73-77 C and reacted for 2h.Concentrated under reduced pressure to, 95g water was added at 45-55C, extracted 4 times 500ml ethyl acetate, the organic layers were combined, dried over anhydrous sodium sulfate 2h, filtered.Ethyl acetate was evaporated under reduced pressure to give 21.2 g of oil. The yield in two steps was 95.0%.

Reference： [1]Patent: CN106588753,2017,A .Location in patent: Paragraph 0016
[2]Patent: CN107200707,2017,A .Location in patent: Paragraph 0017; 0018; 0026; 0027; 0035; 0036; 0045; 0046
[3]Patent: CN113274390,2021,A .Location in patent: Paragraph 0021; 0023
[4]Patent: CN105418460,2016,A .Location in patent: Paragraph 0053; 0060; 0061; 0062; 0063
[5]Patent: WO2014/85362,2014,A1 .Location in patent: Paragraph 0067; 0068; 0069
[6]Patent: WO2017/15272,2017,A1 .Location in patent: Paragraph 0204
[7]Patent: CN109734652,2019,A .Location in patent: Paragraph 0027; 0035; 0037

31
[ 18962-07-7 ]
4-isobutoxybenzylamine acetate [ No CAS ]

Reference： [1]Patent: WO2014/85362,2014,A1

32
[ 18962-07-7 ]
[ 4734-09-2 ]

Reference： [1]Patent: WO2014/85362,2014,A1
[2]Patent: CN105418460,2016,A
[3]Patent: WO2017/15272,2017,A1
[4]Patent: WO2017/15272,2017,A1
[5]Patent: CN106588753,2017,A
[6]Patent: CN107200707,2017,A
[7]Patent: CN113274390,2021,A

33
[ 18962-07-7 ]
[ 639863-75-5 ]

Reference： [1]Patent: WO2014/85362,2014,A1
[2]Patent: CN106588753,2017,A
[3]Patent: CN109734652,2019,A
[4]Journal of Chemical Research,2019,vol. 43,p. 480 - 485

34
[ 551-93-9 ]
[ 18962-07-7 ]
(R)-2-(4-isobutyloxyphenyl)-2,3-dihydroquinolin-4(1H)-one [ No CAS ]
(S)-2-(4-isobutyloxyphenyl)-2,3-dihydroquinolin-4(1H)-one [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2014,vol. 12,p. 9789 - 9792

35
[ 18962-07-7 ]
[ 60974-92-7 ]
C₃₈H₃₈O₂ [ No CAS ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 3403 - 3406

36
[ 18962-07-7 ]
N-(4-isobutoxybenzyl)carbamic acid phenyl ester [ No CAS ]

Reference： [1]Patent: CN105418460,2016,A
[2]Patent: WO2017/15272,2017,A1
[3]Patent: WO2017/15272,2017,A1
[4]Patent: WO2017/15272,2017,A1
[5]Patent: WO2017/15272,2017,A1
[6]Patent: WO2017/15272,2017,A1
[7]Patent: CN107200707,2017,A

37
[ 18962-07-7 ]
4-nitrophenyl (4-isobutoxybenzyl)carbamate [ No CAS ]

Reference： [1]Patent: CN105418460,2016,A

38
[ 18962-07-7 ]
C₁₄H₁₈Cl₃NO₃ [ No CAS ]

Reference： [1]Patent: CN105418460,2016,A

39
[ 13388-75-5 ]
[ 18962-07-7 ]
(Z)-2-(3,5-dimethoxyphenyl)-3-(4-isobutoxyphenyl)acrylonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62.5%		General procedure: A 50 mL round-bottomed flask was charged with 3 (0.177 g, 1 mmol), aromatic aldehyde or substituted aromatic aldehyde (1 mmol) and 10 mL methanol with stirring, and the mixture was heated to 60 C. After 30 min, sodium methoxide (0.027 g, 0.5 mmol) was added to the mixture and keep the temperature for 4-6 h. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to RT, and the precipitate was separated by filter and recrystallized from methanol to give 4a-4z and 5a-5d.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 81 - 85

40
[ 18962-07-7 ]
1-[4-(2-methylpropyloxy)phenyl]methanamino acetate [ No CAS ]

Reference： [1]Patent: WO2017/15272,2017,A1
[2]Patent: CN107011137,2017,A
[3]Patent: CN109734652,2019,A

41
[ 18962-07-7 ]
methyl (4-isobutoxybenzyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2017/15272,2017,A1
[2]Patent: WO2017/15272,2017,A1
[3]Patent: WO2017/15272,2017,A1
[4]Patent: WO2017/15272,2017,A1

42
[ 18962-07-7 ]
2,2,2-trifluoroethyl (4-isobutoxybenzyl)carbamate [ No CAS ]