Name: 97966-31-9|Methyl 3-ethoxy-4-methoxybenzoate|95%
Brand: Ambeed
SKU: A992452
Price: 39.0 USD
Availability: InStock
Rating: 91 (30 reviews)

1
[ 97966-31-9 ]
[ 214470-90-3 ]

Yield	Reaction Conditions	Operation in experiment
	With nitric acid; acetic acid at 50 - 60℃; for 0.75h;
	With cis-nitrous acid In acetic acid at 25 - 55℃; for 0.95h;	Example 59; Methyl 5-Ethoxy-4-methoxy-2-nitrobenzoate A mixture of 15.0 g (74.1 mmol) of methyl 3-ethoxy-4-methoxybenzoate in 45 mL of acetic acid was treated with 15 mL of conc nitric acid dropwise over 12 min. The reaction was kept at 55C for 45 min, cooled to 25C and poured into ice water. The product was extracted into methylene chloride and the extracts were washed with water and dil sodium hydroxide, dried and evaporated. The yield was 17.8 g of methyl 5-ethoxy-4-methoxy-2-nitrobenzoate as yellow crystals: mass spectrum (electrospray, m/e): M+H 256.0.
	With nitric acid

	With nitric acid
	With nitric acid; acetic acid at 55℃; for 1h;	94 A mixture of 15.0 g (74.1 mmol) of methyl 3-ethoxy-4-methoxybenzoate in 45 mL of acetic acid was treated with 15 mL of conc nitric acid dropwise over 12 min. The reaction was kept at 55°C for 45 min, cooled to 25°C and poured into ice water. The product was extracted into methylene chloride and the extracts were washed with water and dil sodium hydroxide, dried and evaporated. The yield was 17.8 g of methyl 5-ethoxy-4-methoxy-2-nitrobenzoate as yellow crystals: mass spectrum (electrospray, m/e): M+H 256.0.

Reference： [1]Wissner; Berger; Boschelli; Brawner Floyd Jr.; Greenberger; Gruber; Johnson; Mamuya; Nilakantan; Reich; Shen; Tsou; Upeslacis; Yu Fen Wang; Wu; Ye; Zhang [Journal of Medicinal Chemistry, 2000, vol. 43, # 17, p. 3244 - 3256]
[2]Current Patent Assignee: PFIZER INC - EP1117659, 2003, B1 Location in patent: Page 60
[3]Current Patent Assignee: SIXERA PHARMA - WO2015/112081, 2015, A1 Location in patent: Page/Page column 15
[4]Current Patent Assignee: SIXERA PHARMA - US2017/2021, 2017, A1 Location in patent: Paragraph 0067
[5]Current Patent Assignee: PFIZER INC - EP973746, 2003, B1 Location in patent: Page/Page column 52

2
[ 6702-50-7 ]
[ 75-03-6 ]
[ 97966-31-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N-methyl-acetamide;	EXAMPLE 95 Methyl 3-Ethoxy-4-methoxybenzoate A mixture of 24.3 g (134 mmol) of methyl <strong>[6702-50-7]3-hydroxy-4-methoxybenzoate</strong>, 36.8 g (267 mmol) of anhyd potassium carbonate and 31.4 g (201 mmol) of ethyl iodide in 500 mL of dimethylformamide was stirred at 100 C. for 5.5 h. An additional amount of ethyl iodide (31.4 g) and potassium carbonate (18.4 g) was added and heating was continued for 2 h more. The reaction was filtered and volatile material was removed from the filtrate in vacuo. The residue was slurried with water and filtered to collect the product which was washed with water and dried. Recrystallization from heptane gave 15.6 g of methyl 3-ethoxy-4-methoxybenzoate as white crystals: mass spectrum (electrospray, m/e): M+H 210.9.
	With potassium carbonate; In N-methyl-acetamide;	EXAMPLE 60 Methyl 3-Ethoxy-4-methoxybenzoate A mixture of 24.3 g (134 mmol) of methyl <strong>[6702-50-7]3-hydroxy-4-methoxybenzoate</strong>, 36.8 g (267 mmol) of anhyd potassium carbonate and 31.4 g (201 mmol) of ethyl iodide in 500 mL of dimethylformamide was stirred at 100 C. for 5.5 h. An additional amount of ethyl iodide (31.4 g) and potassium carbonate (18.4 g) was added and heating was continued for 2 h more. The reaction was filtered and volatile material was removed from the filtrate in vacuo. The residue was slurried with water and filtered to collect the product which was washed with water and dried. Recrystallization from heptane gave 15.6 g of methyl 3-ethoxy-4-methoxybenzoate as white crystals: mass spectrum (electrospray, m/e): M+H 210.9.
	With potassium carbonate; In N-methyl-acetamide;	Example 95 Methyl 3-Ethoxy-4-methoxybenzoate A mixture of 24.3 g (134 mmol) of methyl <strong>[6702-50-7]3-hydroxy-4-methoxybenzoate</strong>, 36.8 g (267 mmol) of anhyd potassium carbonate and 31.4 g (201 mmol) of ethyl iodide in 500 mL of dimethylformamide was stirred at 100C for 5.5 h. An additional amount of ethyl iodide (31.4 g) and potassium carbonate (18.4 g) was added and heating was continued for 2 h more. The reaction was filtered and volatile material was removed from the filtrate in vacuo. The residue was slurried with water and filtered to collect the product which was washed with water and dried. Recrystallization from heptane gave 15.6 g of methyl 3-ethoxy-4-methoxybenzoate as white crystals: mass spectrum (electrospray, m/e): M+H 210.9.

	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 100℃; for 7.5h;	A mixture of 24.3 g (134 mmol) of methyl <strong>[6702-50-7]3-hydroxy-4-methoxybenzoate</strong>, 36.8 g (267 mmol) of anhyd potassium carbonate and 31.4 g (201 mmol) of ethyl iodide in 500 mL of dimethylformamide was stirred at 100C for 5.5 h. An additional amount of ethyl iodide (31.4 g) and potassium carbonate (18.4 g) was added and heating was continued for 2 h more. The reaction was filtered and volatile material was removed from the filtrate in vacuo. The residue was slurried with water and filtered to collect the product which was washed with water and dried. Recrystallization from heptane gave 15.6 g of methyl 3-ethoxy-4-methoxybenzoate as white crystals: mass spectrum (electrospray, m/e): M+H 210.9.
	With potassium carbonate; In N-methyl-acetamide;	PREPARATION 131(2) To a mixture of methyl <strong>[6702-50-7]3-hydroxy-4-methoxybenzoate</strong> (4.00 g) and potassium carbonate (4.55 g) in dimethylformamide (20 mL) was added ethyl iodide (2.63 mL) under water-cooling and the mixture was stirred for 2 hours at ambient temperature. The mixture was partitioned between water and ethyl acetate. The separated organic layer was washed with water and brine, dried over magnesium sulfate and evaporated in vacuo to give methyl 3-ethoxy-4-methoxybenzoate as pale brown powders (4.55 g). NMR (CDCl3, delta): 1.49 (3H, t, J=7 Hz), 3.89 (3H, s), 3.93 (3H, s), 4.16 (2H, q, J=7 Hz), 6.89 (1H, d, J=8 Hz), 7.54 (1H, d, J=4 Hz), 7.66 (1H, dd, J=4, 8 Hz).

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3244 - 3256
[2]Patent: US6002008,1999,A
[3]Patent: US6288082,2001,B1
[4]Patent: EP1263503,2005,B1
[5]Patent: EP1117659,2003,B1 .Location in patent: Page 60
[6]Patent: US6384080,2002,B1
[7]Patent: EP973746,2003,B1 .Location in patent: Page/Page column 52

3
[ 97966-31-9 ]
[ 214470-85-6 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3244 - 3256
[2]Patent: WO2015/112081,2015,A1
[3]Patent: EP973746,2003,B1

4
[ 97966-31-9 ]
[ 214470-75-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: HNO₃; glacial AcOH / 0.75 h / 50 - 60 °C 2.1: Fe; aq. NH₄Cl / methanol / 19 h / Heating 3.1: dimethylformamide / 2.3 h / Heating 4.1: n-BuLi / hexane; tetrahydrofuran / 0.33 h / -78 °C 4.2: hexane; tetrahydrofuran / 1 h / -78 °C 4.3: glacial acetic acid / tetrahydrofuran; hexane / -78 - 25 °C 5.1: oxalyl chloride; DMF / CH₂Cl₂ / 48 h
	Multi-step reaction with 5 steps 1.1: nitric acid; acetic acid / 1 h / 55 °C 2.1: iron; ammonium chloride / methanol; water / 19 h / Heating / reflux 3.1: N,N-dimethyl-formamide / 3 h / Heating / reflux 4.1: n-butyllithium / tetrahydrofuran; hexane / 0.58 h / -78 °C 4.2: 2.5 h 5.1: trichlorophosphate / 3.67 h / Heating / reflux 5.2: pH 8

Reference： [1]Wissner; Berger; Boschelli; Brawner Floyd Jr.; Greenberger; Gruber; Johnson; Mamuya; Nilakantan; Reich; Shen; Tsou; Upeslacis; Yu Fen Wang; Wu; Ye; Zhang [Journal of Medicinal Chemistry, 2000, vol. 43, # 17, p. 3244 - 3256]
[2]Current Patent Assignee: PFIZER INC - EP973746, 2003, B1

5
[ 97966-31-9 ]
[ 214470-78-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: HNO₃; glacial AcOH / 0.75 h / 50 - 60 °C 2.1: Fe; aq. NH₄Cl / methanol / 19 h / Heating 3.1: dimethylformamide / 2.3 h / Heating 4.1: n-BuLi / hexane; tetrahydrofuran / 0.33 h / -78 °C 4.2: hexane; tetrahydrofuran / 1 h / -78 °C 4.3: glacial acetic acid / tetrahydrofuran; hexane / -78 - 25 °C
	Multi-step reaction with 4 steps 1.1: nitric acid; acetic acid / 1 h / 55 °C 2.1: iron; ammonium chloride / methanol; water / 19 h / Heating / reflux 3.1: N,N-dimethyl-formamide / 3 h / Heating / reflux 4.1: n-butyllithium / tetrahydrofuran; hexane / 0.58 h / -78 °C 4.2: 2.5 h

Reference： [1]Wissner; Berger; Boschelli; Brawner Floyd Jr.; Greenberger; Gruber; Johnson; Mamuya; Nilakantan; Reich; Shen; Tsou; Upeslacis; Yu Fen Wang; Wu; Ye; Zhang [Journal of Medicinal Chemistry, 2000, vol. 43, # 17, p. 3244 - 3256]
[2]Current Patent Assignee: PFIZER INC - EP973746, 2003, B1

6
[ 97966-31-9 ]
[ 1026844-87-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: HNO₃; glacial AcOH / 0.75 h / 50 - 60 °C 2: Fe; aq. NH₄Cl / methanol / 19 h / Heating 3: dimethylformamide / 2.3 h / Heating

Reference： [1]Wissner; Berger; Boschelli; Brawner Floyd Jr.; Greenberger; Gruber; Johnson; Mamuya; Nilakantan; Reich; Shen; Tsou; Upeslacis; Yu Fen Wang; Wu; Ye; Zhang [Journal of Medicinal Chemistry, 2000, vol. 43, # 17, p. 3244 - 3256]

7
[ 97966-31-9 ]
4-(3-bromophenylamino)-6-ethoxy-7-methoxyquinoline-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: HNO₃; glacial AcOH / 0.75 h / 50 - 60 °C 2.1: Fe; aq. NH₄Cl / methanol / 19 h / Heating 3.1: dimethylformamide / 2.3 h / Heating 4.1: n-BuLi / hexane; tetrahydrofuran / 0.33 h / -78 °C 4.2: hexane; tetrahydrofuran / 1 h / -78 °C 4.3: glacial acetic acid / tetrahydrofuran; hexane / -78 - 25 °C 5.1: oxalyl chloride; DMF / CH₂Cl₂ / 48 h 6.1: 86 percent / 2-ethoxy-ethanol / 3 h / Heating
	Multi-step reaction with 6 steps 1.1: nitric acid; acetic acid / 1 h / 55 °C 2.1: iron; ammonium chloride / methanol; water / 19 h / Heating / reflux 3.1: N,N-dimethyl-formamide / 3 h / Heating / reflux 4.1: n-butyllithium / tetrahydrofuran; hexane / 0.58 h / -78 °C 4.2: 2.5 h 5.1: trichlorophosphate / 3.67 h / Heating / reflux 5.2: pH 8 6.1: ethanol / 7 h / Heating / reflux

Reference： [1]Wissner; Berger; Boschelli; Brawner Floyd Jr.; Greenberger; Gruber; Johnson; Mamuya; Nilakantan; Reich; Shen; Tsou; Upeslacis; Yu Fen Wang; Wu; Ye; Zhang [Journal of Medicinal Chemistry, 2000, vol. 43, # 17, p. 3244 - 3256]
[2]Current Patent Assignee: PFIZER INC - EP973746, 2003, B1

8
[ 645-08-9 ]
[ 97966-31-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: anschliessende Hydrolyse
	Multi-step reaction with 2 steps 1: sulfuric acid / methanol 2: potassium carbonate / <i>N</i>-methyl-acetamide
	Multi-step reaction with 2 steps 1: sulfuric acid / Heating / reflux 2: potassium carbonate / N,N-dimethyl-formamide / 7.5 h / 100 °C

Multi-step reaction with 2 steps 1: sulfuric acid / 65 °C 2: potassium carbonate / acetone / 6.5 h / 60 °C

Reference： [1]Freudenberg et al. [Chemische Berichte, 1939, vol. 72, p. 217,226]
[2]Current Patent Assignee: ASTELLAS PHARMA INC. - US6384080, 2002, B1
[3]Current Patent Assignee: PFIZER INC - EP973746, 2003, B1
[4]Current Patent Assignee: CHANGZHOU UNIVERSITY - CN108752248, 2018, A

9
[ 6702-50-7 ]
[ 100-39-0 ]
[ 57535-57-6 ]
[ 97966-31-9 ]

Yield	Reaction Conditions	Operation in experiment
		PREPARATION 146(1) Methyl 3-benzyloxy-4-methoxybenzoate (5.70 g) was obtained as colorless powders from methyl 3-hydroxy-4-methoxybenzoate (4.00 g) and benzyl bromide (3.13 mL) in a manner similar to Preparation 131(2). NMR (CDCl3, δ): 3.87 (3H, s), 3.93 (3H, s), 5.18 (2H, s), 6.90 (1H, d, J=8 Hz), 7.28-7.40 (3H, m), 7.46 (2H, m), 7.61 (1H, d, J=4 Hz), 7.68 (1H, dd, J=4, 8 Hz).

Reference： [1]Patent: US6384080,2002,B1

10
[ 617-05-0 ]
[ 6482-24-2 ]
[ 196194-41-9 ]
[ 97966-31-9 ]

Yield	Reaction Conditions	Operation in experiment
		PREPARATION 134(1) Ethyl 3-methoxy-4-(2-methoxyethoxy)benzoate (5.69 g) was obtained as colorless powders from <strong>[617-05-0]ethyl 4-hydroxy-3-methoxybenzoate</strong> (5.00 g) and 2-methoxyethyl bromide (3.59 mL) in a manner similar to Preparation 131(2). NMR (CDCl3, delta): 1.39 (3H, t, J=7 Hz), 3.46 (3H, s), 3.81 (2H, t, J=4 Hz), 3.91 (3H, s), 4.23 (2H, t, J=4 Hz), 4.35 (2H, q, J=7 Hz), 6.91 (1H, d, J=8 Hz), 7.55 (1H, d, J=4 Hz), 7.65 (1H, dd, J=4, 8 Hz).

Reference： [1]Patent: US6384080,2002,B1

11
[ 3943-74-6 ]
[ 75-03-6 ]
[ 3535-24-8 ]
[ 97966-31-9 ]

Yield	Reaction Conditions	Operation in experiment
		133.2 PREPARATION 133(2) PREPARATION 133(2) Methyl 4-ethoxy-3-methoxybenzoate (4.10 g) was obtained as colorless powders from methyl 4-hydroxy-3-methoxybenzoate (4.00 g) and ethyl iodide (2.63 mL) in a manner similar to Preparation 131(2). NMR (CDCl3, δ): 1.50 (3H, t, J=7 Hz), 3.89 (3H, s), 3.93 (3H, s), 4.14 (2H, q, J=7 Hz), 6.88 (1H, d, J=8 Hz), 7.54 (1H, d, J=4 Hz), 7.65 (1H, dd, J=4, 8 Hz).

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - US6384080, 2002, B1

12
conc nitric acid [ No CAS ]
[ 97966-31-9 ]
[ 214470-90-3 ]

Yield	Reaction Conditions	Operation in experiment
	In acetic acid	94 Methyl 5-Ethoxy-4-methoxy-2-nitrobenzoate EXAMPLE 94 Methyl 5-Ethoxy-4-methoxy-2-nitrobenzoate A mixture of 15.0 g (74.1 mmol) of methyl 3-ethoxy-4-methoxybenzoate in 45 mL of acetic acid was treated with 15 mL of conc nitric acid dropwise over 12 min. The reaction was kept at 55° C. for 45 min, cooled to 25° C. and poured into ice water. The product was extracted into methylene chloride and the extracts were washed with water and dil sodium hydroxide, dried and evaporated. The yield was 17.8 g of methyl 5-ethoxy-4-methoxy-2-nitrobenzoate as yellow crystals: mass spectrum (electrospray, m/e): M+H 256.0.
	In acetic acid	94 Methyl 5-Ethoxy-4-methoxy-2-nitrobenzoate EXAMPLE 94 Methyl 5-Ethoxy-4-methoxy-2-nitrobenzoate A mixture of 15.0 g (74.1 mmol) of methyl 3-ethoxy-4-methoxybenzoate in 45 mL of acetic acid was treated with 15 mL of conc nitric acid dropwise over 12 min. The reaction was kept at 55° C. for 45 min, cooled to 25° C. and poured into ice water. The product was extracted into methylene chloride and the extracts were washed with water and μl sodium hydroxide, dried and evaporated. The yield was 17.8 g of methyl 5-ethoxy-4-methoxy-2-nitrobenzoate as yellow crystals: mass spectrum (electrospray, m/e): M+H 256.0.
	In acetic acid	59 Methyl 5-Ethoxy-4-methoxy-2-nitrobenzoate EXAMPLE 59 Methyl 5-Ethoxy-4-methoxy-2-nitrobenzoate A mixture of 15.0 g (74.1 mmol) of methyl 3-ethoxy-4-methoxybenzoate in 45 mL of acetic acid was treated with 15 mL of conc nitric acid dropwise over 12 min. The reaction was kept at 55° C. for 45 min, cooled to 25° C. and poured into ice water. The product was extracted into methylene chloride and the extracts were washed with water and dil sodium hydroxide, dried and evaporated. The yield was 17.8 g of methyl 5-ethoxy-4-methoxy-2-nitrobenzoate as yellow crystals: mass spectrum (electrospray, m/e): M+H 256.0.

In acetic acid

94 Methyl 5-Ethoxy-4-methoxy-2-nitrobenzoate Example 94 Methyl 5-Ethoxy-4-methoxy-2-nitrobenzoate A mixture of 15.0 g (74.1 mmol) of methyl 3-ethoxy-4-methoxybenzoate in 45 mL of acetic acid was treated with 15 mL of conc nitric acid dropwise over 12 min. The reaction was kept at 55°C for 45 min, cooled to 25°C and poured into ice water. The product was extracted into methylene chloride and the extracts were washed with water and dil sodium hydroxide, dried and evaporated. The yield was 17.8 g of methyl 5-ethoxy-4-methoxy-2-nitrobenzoate as yellow crystals: mass spectrum (electrospray, m/e): M+H 256.0.

Reference： [1]Current Patent Assignee: PFIZER INC - US6384051, 2002, B1
[2]Current Patent Assignee: PFIZER INC - US6002008, 1999, A
[3]Current Patent Assignee: PFIZER INC - US6288082, 2001, B1
[4]Current Patent Assignee: PFIZER INC - EP1263503, 2005, B1

13
IN-sodium hydroxide [ No CAS ]
[ 97966-31-9 ]
[ 2651-55-0 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol	131.3 PREPARATION 131(3) PREPARATION 131(3) A mixture of methyl 3-ethoxy-4-methoxybenzoate (4.42 g), methanol (160 mL) and IN-sodium hydroxide solution (40 mL) was heated for 2 hours under reflux. The reaction mixture was acidified with 1N-hydrochloric acid to pH 4, and the organic solvent was removed by evaporation. The aqueous layer was diluted with water and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was triturated with hexane to give 3-ethoxy-4-methoxybenzoic acid as colorless powders (3.76 g). NMR (CDCl3, δ): 1.50 (3H, t, J=7 Hz), 3.95 (3H, s), 4.17 (2H, q, J=7 Hz), 6.92 (1H, d, J=8 Hz), 7.60 (1H, d, J=4 Hz), 7.76 (1H, dd, J=4, 8 Hz); Mass m/z: 195(M+).

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - US6384080, 2002, B1

14
[ 97966-31-9 ]
6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: nitric acid 2: iron; ammonium chloride 3: thionyl chloride 4: potassium hydroxide 5: thionyl chloride / N,N-dimethyl-formamide
	Multi-step reaction with 5 steps 1: nitric acid 2: iron; ammonium chloride 3: thionyl chloride 4: potassium hydroxide 5: thionyl chloride / N,N-dimethyl-formamide

Reference： [1]Current Patent Assignee: SIXERA PHARMA - WO2015/112081, 2015, A1
[2]Current Patent Assignee: SIXERA PHARMA - US2017/2021, 2017, A1

15
[ 74-96-4 ]
[ 6702-50-7 ]
[ 97966-31-9 ]

Yield	Reaction Conditions	Operation in experiment
95.9%	With potassium carbonate; In acetone; at 60℃; for 4.5h;Sealed tube;	Step 1: Methyl 3-ethoxy-4-methoxybenzoate[0576]To a solution of methyl <strong>[6702-50-7]3-hydroxy-4-methoxybenzoate</strong> (10 g, 54.94 mmol) in acetone (50 mL) were added anhydrous potassium carbonate (15.2 g, 110.0 mmol) and bromoethane (6.1 mL, 82.42 mmol) in turn. The whole mixture was stirred at 60 in a sealed tube for 4.5 hours. To the reaction mixture was added 20 mL of saturated aqueous sodium chloride, and the mixture was extracted with ethyl acetate (25 mL × 3) . The organic layers were combined, dried over anhydrous sodium sulfate for 1 hour, and the solvent was removed to give the title compound as a white solid (11.07 g, 95.9) .[0577]1H NMR (400 MHz, CDCl3) : delta ppm 7.65 (d, J 8.4 Hz, 1H) , 7.53 (s, 1H) , 6.87 (d, J 8.4 Hz, 1H ) , 4.12-4.17 (m, 2H) , 3.91 (s, 3H) , 3.87 (s, 3H) , 1.47 (t, J 7.0 Hz, 3H) and MS-ESI: m/z 211.2 [M+H]+.
88%	With potassium carbonate; In acetone; at 60℃; for 6.5h;	10 g of methyl <strong>[6702-50-7]3-hydroxy-4-methoxybenzoate</strong>, 14.94 g of potassium carbonate, 8.83 g of ethyl bromide and 200 mL of acetone were successively added to a dry 250 mL three-necked flask, and the mixture was heated to 60 C, and reacted under magnetic stirring for 4.5 hours. Further, 8.83 g of ethyl bromide was added at the reaction for 2 hours. After the end of the reaction, the product was collected into a 250 ml round bottom flask, and mixed with 77 mL of saturated brine and 48 mL of ethyl acetate. The filtrate was recovered, and then extracted with 48 mL of ethyl acetate. The organic phase was distilled under reduced pressure to give a solid product. Methyl oxy-4-methoxybenzoate 9.44 g, yield 88.0%.

Reference： [1]Patent: WO2015/161830,2015,A1 .Location in patent: Paragraph 00301
[2]Patent: CN108752248,2018,A .Location in patent: Page/Page column 6-8

16
[ 97966-31-9 ]
(S)-tert-butyl (1-(4-(((3,5-dichloropyridin-4-yl)methyl)carbamoyl)-2-(3-ethoxy-4-methoxyphenyl)oxazol-5-yl)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: water; sodium hydroxide / ethanol / 1.5 h / 60 °C 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 1-hydroxy-7-aza-benzotriazole / dichloromethane / 0.5 h / 20 °C 2.2: 20 °C / Cooling with ice 3.1: Lawessons reagent / tetrahydrofuran / 2 h / 75 °C 4.1: dichloromethane / 3 h / -78 - 0 °C 5.1: potassium hexamethylsilazane / tetrahydrofuran / 1 h / -78 °C 6.1: water; lithium hydroxide monohydrate / tetrahydrofuran / 3 h / 40 °C 7.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 1-hydroxy-7-aza-benzotriazole / dichloromethane / 0.5 h / 0 °C 7.2: 22 h / 20 °C