[ CAS No. 873055-57-3 ] {[proInfo.proName]}

Name: 873055-57-3|2,4-Di-tert-butyl-5-nitrophenol|98%
Brand: Ambeed
SKU: A285897
Rating: 97 (32 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

2D 3D

Structure of 873055-57-3 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 873055-57-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 873055-57-3 ]

SDS Specification

Alternatived Products of [ 873055-57-3 ]

Product Details of [ 873055-57-3 ]

CAS No. :	873055-57-3	MDL No. :	MFCD11052606
Formula :	C₁₄H₂₁NO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VIWYWRSFQRIVPI-UHFFFAOYSA-N
M.W :	251.32	Pubchem ID :	44176225
Synonyms :

Safety of [ 873055-57-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 873055-57-3 ]

* 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 [ 873055-57-3 ]
Downstream synthetic route of [ 873055-57-3 ]

[ 873055-57-3 ] Synthesis Path-Upstream 1~6

1
[ 96-76-4 ]
[ 873055-57-3 ]

Yield	Reaction Conditions	Operation in experiment
92.3%	With sulfuric acid; nitric acid In dichloromethane at 0 - 10℃; for 1 h;	Weighed compound 1 (20.6 g, 0.1mol) in 250 mL three-necked flask, 100 mL of dichloromethane was added, Control the temperature at 5 °C to 10 °C, a 1:1 mixture of 12 mL of concentrated sulfuric acid and concentrated nitric acid was added dropwise. Drop finished, The control temperature was stirred at 0 °C-5 °C for 1 h. After the reaction is completed, the reaction system is directly added to the ice water, Stirred for 5 minutes, allowed to stand, The aqueous phase was extracted twice with dichloromethane, The combined methylene chloride layer, Washed twice with saturated aqueous sodium chloride solution, Dried over anhydrous sodium sulfate, filtered, The filtrate was concentrated under reduced pressure to give compound 2 in an amount of 23.2 g, yield 92.3percent.

Reference： [1] Patent: CN103787968, 2016, B, . Location in patent: Paragraph 0039; 0044; 0045
[2] Patent: WO2014/118805, 2014, A1,
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 9776 - 9795
[4] Patent: US2015/231142, 2015, A1,
[5] Patent: US2011/98311, 2011, A1,
[6] Patent: US2011/98311, 2011, A1,
[7] Patent: US2017/96397, 2017, A1,
[8] Patent: WO2018/107100, 2018, A1,

2
[ 873055-54-0 ]
[ 873055-57-3 ]
[ 20039-94-5 ]

Yield	Reaction Conditions	Operation in experiment
29%	Stage #1: at 50℃; for 2 h; Cooling with ice Stage #2: With potassium hydroxide In methanol at 20℃; for 2 h;	To a stirring mixture of carbonic acid 2,4-di-tert-butyl-phenyl ester methyl ester (4.76 g, 18 mmol) in conc. sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50° C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgSO₄), concentrated and purified by column chromatography (0-10percent ethyl acetate-hexanes) to yield a mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step. 2,4--Di-tert-butyl-5-nitro-phenol and 2,4-Di-tert-butyl-6-nitro-phenol (0515) The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 12.9 mmol) was dissolved in MeOH (65 mL) and KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding conc. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO₄), concentrated and purified by column chromatography (0-5percent ethyl acetate-hexanes) to provide 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29percent over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tert-butyl-5-nitro-phenol: ¹H NMR (400 MHz, DMSO-d₆) δ 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitro-phenol: ¹H NMR (400 MHz, CDCl₃) δ 11.48 (s, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
1.31 g	Stage #1: at 20 - 50℃; for 2 h; Stage #2: at 20℃; for 2 h;	To a stirring mixture of carbonic acid 2,4-di-tert-butyl-phenyl ester methyl ester (4.76 g, 180 mmol) in conc. sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50° C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgSO₄), concentrated and purified by column chromatography (0-10percent ethyl acetate hexanes) to yield a mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step. Step C: 2,4-Di-tert-butyl-5-nitro-phenol and 2,4-Di-tert-butyl-6-nitro-phenol (0101) The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in 50 MeOH (65 mL) before 51 KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding cone. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO₄), concentrated and purified by column chromatography (0-5percent ethyl acetate-hexanes) to provide 52 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29percent over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tert-butyl-5-nitro-phenol: ¹H NMR (400 MHz, DMSO-d6) δ 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H) ppm. 2,4-Di-tert-butyl-6-nitro-phenol: ¹H NMR (400 MHz, CDCl₃) δ 11.48 (s, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H) ppm.

Reference： [1] Patent: US2015/231142, 2015, A1, . Location in patent: Paragraph 0514; 0515
[2] Patent: US2010/168094, 2010, A1, . Location in patent: Page/Page column 72; 73
[3] Patent: WO2018/64632, 2018, A1, . Location in patent: Paragraph 00217; 00221; 00222; 00223
[4] Patent: WO2018/107100, 2018, A1, . Location in patent: Paragraph 00236; 00239; 00240
[5] Patent: US2018/280349, 2018, A1, . Location in patent: Paragraph 0098; 0100-0101

3
[ 873055-55-1 ]
[ 873055-56-2 ]
[ 873055-57-3 ]
[ 20039-94-5 ]

Yield	Reaction Conditions	Operation in experiment
29%	With hydrogenchloride; KOH In methanol	2,4-Di-tert-butyl-5-nitro-phenol and 2,4-Di-tert-butyl-6-nitro-phenol The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 12.9 mmol) was dissolved in MeOH (65 mL) and KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding conc. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO₄), concentrated and purified by column chromatography (0-5percent ethyl acetate-hexanes) to provide 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29percent over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tert-butyl-5-nitro-phenol: ¹H NMR (400 MHz, DMSO-d₆) δ 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitro-phenol: ¹H NMR (400 MHz, CDCl₃) δ 11.48 (s, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).

Reference： [1] Patent: US2011/98311, 2011, A1,
[2] Patent: US2008/90864, 2008, A1, . Location in patent: Page/Page column 8
[3] Patent: WO2007/79139, 2007, A2, . Location in patent: Page/Page column 47; 48

4
[ 873055-55-1 ]
[ 873055-57-3 ]

Reference： [1] Patent: WO2014/118805, 2014, A1, . Location in patent: Paragraph 0287
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 9776 - 9795

5
[ 873055-54-0 ]
[ 873055-57-3 ]

Reference： [1] Patent: US2011/98311, 2011, A1,
[2] Patent: US2011/98311, 2011, A1,
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 9776 - 9795

6
[ 96-76-4 ]
[ 873055-57-3 ]
[ 20039-94-5 ]

Reference： [1] Patent: WO2018/64632, 2018, A1,
[2] Patent: US2018/280349, 2018, A1,

[ 873055-57-3 ] Synthesis Path-Downstream 1~23

1
[ 873055-55-1 ]
[ 873055-56-2 ]
[ 873055-57-3 ]
[ 20039-94-5 ]

Yield	Reaction Conditions	Operation in experiment
29%	With hydrogenchloride; KOH; In methanol;	2,4-Di-tert-butyl-5-nitro-phenol and 2,4-Di-tert-butyl-6-nitro-phenol The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 12.9 mmol) was dissolved in MeOH (65 mL) and KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding conc. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-5% ethyl acetate-hexanes) to provide 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tert-butyl-5-nitro-phenol: 1H NMR (400 MHz, DMSO-d6) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitro-phenol: 1H NMR (400 MHz, CDCl3) delta 11.48 (s, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
		2,4-Di-tert-butyl-5-nitro-phenol and 2,4-Di-tert-butyl-6-nitro-phenol The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding conc. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-5% ethyl acetate-hexanes) to provide 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tert-butyl-5-nitro-phenol: 1H NMR (400 MHz, DMSO-d6) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitro-phenol: 1H NMR (400 MHz, CDCl3) delta 11.48 (s, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
		[0226] The mixture of carbonic acid 2,4-di-ter£-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-ter?-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding cone. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0 - 5 % ethyl acetate - hexanes) to provide 2,4-di-fe/Y-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert- butyl-6-nitro-phenol. 2,4-Di-tert-butyl-5-nitro-phenol: 1H NMR (400 MHz, DMSO-fe) delta 10.14 (s, IH, OH), 7.34 (s, IH), 6.83 (s, IH)5 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6- nitro-phenol: 1H NMR (400 MHz, CDCl3) delta 11.48 (s, IH), 7.98 (d, J = 2.5 Hz, IH), 7.66 (d, J = 2.4 Hz, IH), 1.47 (s, 9H), 1.34 (s, 9H).

Reference： [1]Patent: US2011/98311,2011,A1
[2]Patent: US2008/90864,2008,A1 .Location in patent: Page/Page column 8
[3]Patent: WO2007/79139,2007,A2 .Location in patent: Page/Page column 47; 48

2
[ 873055-57-3 ]
[ 873055-58-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With ammonium formate;5%-palladium/activated carbon; In ethanol; for 2h;Heating / reflux;	5-Amino-2,4-di-tert-butyl-phenol To a reluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitro-phenol</strong> (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99% CH3CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With ammonium formate;palladium on carbon; In ethanol; for 2h;Reflux;	C-9; 5-Amino-2,4-di-tert-butyl-phenol: To a reluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitro-phenol</strong> (1.86 g, 7.4 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99% CH3CN, 5 min run; ESI-MS 222.4 m/z (MH+)
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a refluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitro-phenol</strong> (1.86 g, 7.4 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99% CH3CN, 5 min run; ESI-MS 222.4 m/z (MH+).

100%	With ammonium formate;5% palladium over charcoal; In ethanol; for 2h;Heating / reflux;	[0228] To a reluxing solution of 2,4-di-t°?-butyl-5-nit?>phenol (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-ter£-butyl-phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz5 DMSO-^6) delta 8.64 (s, IH, OH), 6.84 (s, IH)5 6.08 (s, IH)5 4.39 (s, 2H, NH2), <n="51"/>1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99 % CH3CN, 5 min ran; ESI-MS 222.4 m/z [M+H]+.
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a refluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitro-phenol</strong> (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant). 1H NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 mm, 10-99 % CH3CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With palladium on activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a refluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitro-phenol</strong> (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant.).1H NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99 % CH3CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	Step D: 5-Amino-2,4-di-tert-butyl-phenol To a refluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitro-phenol</strong> (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H) ppm; HPLC ret. time 2.72 min, 10-99% CH3CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	1003411 To a refluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitro-phenol</strong> (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant.). ?HNIVIR (400 IVIFIz, DMSO-d6) 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 mm, 10-99 % CH3CN, 5 mm run; ESI-MS 222.4 m/z [M+H]t
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a refluxing solution of 2,4-di-ieri-butyl-5-nitro-phenol (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-ie/ -butyl-phenol as a grey solid (1.66 g, quant.). lH NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99 % CH3CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a refluxing solution of 2,4-di-ieri-butyl-5-nitro-phenol (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-ie/ -butyl-phenol as a grey solid (1.66 g, quant.). lH NMR (400 MHz, DMSO-ifc) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99 % CH3CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a reluxing solution of 2,4-di-ieri-butyl-5-nitro-phenol (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-ie/ -butyl-phenol as a grey solid (1.66 g, quant.). lH NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99 % (1131) CH3CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a refluxing solution of 2,4-di-ie/T-butyl-5-nitro-phenol (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5 -amino-2, 4-di-ie/T-butyl-phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz, DMSO-d6) d 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99 % CH CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a refluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitro-phenol</strong> (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99% CH3CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a refluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitrophenol</strong> (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz, DMSO-rfc) d 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99 % CH3CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a refluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitro-phenol</strong> (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99% CH3CN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
100%	With 5%-palladium/activated carbon; ammonium formate; In ethanol; for 2h;Reflux;	To a reluxing solution of 2,4-di-/er/-butyl-5-nitro-phenol (1.86 g, 7.40 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-/c77-butyl -phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz, DMSO-^e) d 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99 % (0434) CftCN, 5 min run; ESI-MS 222.4 m/z [M+H]+.
	With palladium 10% on activated carbon; hydrogen; In methanol; at 25 - 30℃; for 2h;	In a clean round bottom flask charge, 2,4-di-tert-butyl-5-nitrophenyl methyl carbonate (10.0 gm) and potassium hydroxide ( 2.71 gm) in 60.0 ml of methanol. The reaction mass was stirred for 2- 3 hr and concentrated. To the residue water and ethyl acetate was added and pH was adjusted to 1.0 to 3.0 by con HC1. The organic layer was washed with 10 % sodium chloride solution and then concentrated ethyl acetate toe get solid. The solid was dissolved in 50.0 ml of methanol and charge 10 % palladium carbon (0.37 gm) in hydrogenater. To this a 5.0 to 6.0 kg Hydrogen pressure was applied and maintained for 2.0 hr at 25- 30. The reaction mass was filtered and 50.0 ml water was added and maintained for 2.0 hr at 25-30 C. The reaction mass was filtered and purified with 40.0 ml of n-hexane to get 6.0 gm of title product. Chromatographic purity by HPLC 99.98 %
	With hydrogen; In isopropyl alcohol; at 20℃; under 3000.3 - 4500.45 Torr;	Example-4 Preparation of 2, 4 di-tert-butyl-5-aminophenol Method-A: 2, 4 di-tert-butyl-5-nitro phenol (100 g) was dissolved in isopropyl alcohol (400 ml) at room temperature and charged to an autoclave vessel. Charge 20 grams Raney Nickel. (Previously washed with water and dried with isopropyl alcohol). The vessel was fitted on an autoclave and flushed with hydrogen gas twotirnes. The reaction mass maintained under hydrogen gas pressure (4-6 kg) at room temperature for 90-240 minutes. The progress of reaction mass was monitored by TLC (The starting material nitro compound was below 0.5%). After completion of the reaction, the Raney nickel catalyst was separated by filtration and the hyflo bed was washed with isopropyl alcohol (100 ml). The filtrate was charged to the RB flask and water (1000 ml) was added drop wise in 60-90 minutes at 20-25 C. The slurry was maintained under stirring for 60-90 minutes at same temperature. The crude product was collected by filtration and washed with water (100-200 ml). The wet solid obtained was dried in air oven for 4 hours at 45-50 C. The semidry solid was taken in Toluene (200 ml) and the reaction mass was heated to 70-80 C.; maintained at 70-80 C. for 60 minutes and then cooled to 0-5 C. The slurry was stirred at 0-5 C. for 60-90 minutes. The resultant solid was filtered, washed with chilled toluene (50 ml) and dried at 45-50 C. for 6-8 hours to obtain the title compound (55-70 grams) as light pink colored crystalline solid.

Reference： [1]Patent: US2008/90864,2008,A1 .Location in patent: Page/Page column 8
[2]Patent: US2010/168094,2010,A1 .Location in patent: Page/Page column 72; 73
[3]Journal of Medicinal Chemistry,2014,vol. 57,p. 9776 - 9795
[4]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 0516
[5]Patent: WO2007/79139,2007,A2 .Location in patent: Page/Page column 47-49
[6]Patent: WO2018/64632,2018,A1 .Location in patent: Paragraph 00217; 00224; 00225
[7]Patent: WO2018/107100,2018,A1 .Location in patent: Paragraph 00236; 00243; 00244
[8]Patent: US2018/280349,2018,A1 .Location in patent: Paragraph 0098; 0102
[9]Patent: WO2019/10092,2019,A1 .Location in patent: Paragraph 00324; 00325; 00333; 00340; 00341
[10]Patent: WO2019/18353,2019,A1 .Location in patent: Paragraph 00151
[11]Patent: WO2019/18395,2019,A1 .Location in patent: Paragraph 00182
[12]Chemistry - A European Journal,2019,vol. 25,p. 3662 - 3674
[13]Patent: WO2018/227049,2018,A1 .Location in patent: Paragraph 00208; 00215; 00216
[14]Patent: WO2019/113089,2019,A1 .Location in patent: Paragraph 00249
[15]Patent: US2019/119253,2019,A1 .Location in patent: Paragraph 0516; 0520
[16]Patent: WO2019/191620,2019,A1 .Location in patent: Paragraph 00430
[17]Patent: US2019/240197,2019,A1 .Location in patent: Paragraph 0575; 0579
[18]Patent: WO2020/102346,2020,A1 .Location in patent: Paragraph 00121
[19]Patent: WO2014/118805,2014,A1 .Location in patent: Paragraph 0287
[20]Patent: US2017/96397,2017,A1 .Location in patent: Paragraph 0087; 0088

3
[ 873055-57-3 ]
[ 7440-44-0 ]
[ 873055-58-4 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium formate; In ethanol;	C-9; 5-Amino-2,4-di-tert-butyl-phenol To a reluxing solution of <strong>[873055-57-3]2,4-di-tert-butyl-5-nitro-phenol</strong> (1.86 g, 7.4 mmol) and ammonium formate (1.86 g) in ethanol (75 mL) was added Pd-5% wt. on activated carbon (900 mg). The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and filtered through Celite. The Celite was washed with methanol and the combined filtrates were concentrated to yield 5-amino-2,4-di-tert-butyl-phenol as a grey solid (1.66 g, quant.). 1H NMR (400 MHz, DMSO-d6) delta 8.64 (s, 1H, OH), 6.84 (s, 1H), 6.08 (s, 1H), 4.39 (s, 2H, NH2), 1.27 (m, 18H); HPLC ret. time 2.72 min, 10-99% CH3CN, 5 min run; ESI-MS 222.4 m/z (MH+).

Reference： [1]Patent: US2011/98311,2011,A1

4
[ 873055-54-0 ]
[ 873055-57-3 ]
[ 20039-94-5 ]

Yield	Reaction Conditions	Operation in experiment
29%		To a stirring mixture of carbonic acid 2,4-di-tert-butyl-phenyl ester methyl ester (4.76 g, 18 mmol) in conc. sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50 C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-10% ethyl acetate-hexanes) to yield a mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step. 2,4--Di-tert-butyl-5-nitro-phenol and 2,4-Di-tert-butyl-6-nitro-phenol (0515) The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 12.9 mmol) was dissolved in MeOH (65 mL) and KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding conc. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-5% ethyl acetate-hexanes) to provide 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tert-butyl-5-nitro-phenol: 1H NMR (400 MHz, DMSO-d6) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitro-phenol: 1H NMR (400 MHz, CDCl3) delta 11.48 (s, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
29%		The mixture of carbonic acid 2,4-di-ieri-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-ieri-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding cone. HC1 and partitioned between water and diethyl ether. The ether layer was dried (MgS04), concentrated and purified by column chromatography (0 - 5 % ethyl acetate - hexanes) to provide 2,4-di-ieri-butyl-5-nitro- phenol (1.31 g, 29% over 2 steps) and 2,4-di-ieri-butyl-6-nitro-phenol. 2,4-Di-ie/ -butyl- 5-nitro-phenol: lH NMR (400 MHz, DMSO-d6) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-ieri-butyl-6-nitro-phenol: lH NMR (400 MHz, CDCb) delta 11.48 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
29%		The mixture of carbonic acid 2,4-di-ieri-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-ieri-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding cone. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgS04), concentrated and purified by column chromatography (0 - 5 % ethyl acetate - hexanes) to provide 2,4-di-ieri-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-ieri-butyl-6-nitro-phenol. 2,4-Di-ieri-butyl-5-nitro-phenol: XH NMR (400 MHz, DMSO-ifc) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-ieri-butyl-6-nitro-phenol: lH NMR (400 MHz, CDC13) delta 11.48 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).

29%		Carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and Carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester To a stirring mixture of carbonic acid 2,4-di-ie/ -butyl-phenyl ester methyl ester (4.76 g, 180 mmol) in cone, sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50 C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgS04), concentrated and purified by column chromatography (0 - 10% ethyl acetate - hexanes) to yield a mixture of carbonic acid 2,4-di-ieri-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-ieri-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step. Step 3: 2,4-Di-tert-butyl-5-nitro-phenol and 2,4-Di-tert-butyl-6-nitro-phenol (1128) [00214] The mixture of carbonic acid 2,4-di-ieri-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-ieri-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding cone. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgS04), concentrated and purified by column chromatography (0 - 5 % ethyl acetate - hexanes) to provide 2,4-di-ieri-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-ieri-butyl-6-nitro-phenol. 2,4-Di-ieri-butyl-5-nitro-phenol: XH NMR (400 MHz, DMSO-ifc) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-ieri-butyl-6-nitro-phenol: lH NMR (400 MHz, CDC13) delta 11.48 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
29%		To a stirring mixture of carbonic acid 2,4-di-ie/ -butyl-phenyl ester methyl ester (4.76 g, 180 mmol) in cone sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50 C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgS04), concentrated and purified by column chromatography (0 - 10% ethyl acetate - hexanes) to yield a mixture of carbonic acid 2,4-di-ie/ -butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-/er/-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step.Step 3: 2,4-Di-tert-butyl-5-nitrophenol and 2,4-Di-tert-butyl-6-nitrophenol [00429] The mixture of carbonic acid 2,4-di-tert-butyl-5-nitrophenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitrophenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding cone. HC1 and partitioned between water and diethyl ether. The ether layer was dried (MgS04), concentrated and purified by column chromatography (0 - 5 % ethyl acetate - hexanes) to provide 2,4-di-tert-butyl-5-nitrophenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6-nitrophenol. 2,4-Di-tert-butyl-5-nitrophenol : 1H NMR (400 MHz, DMSO-rfc) d 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitrophenol: 1H NMR (400 MHz, CDCb) d 11.48 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
29%		To a stirring mixture of carbonic acid 2,4-di-tert-butyl-phenyl ester methyl ester (4.76 g, 180 mmol) in conc. sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50 C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-10% ethyl acetate-hexanes) to yield a mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step. The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding conc. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-5% ethyl acetate-hexanes) to provide 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tert-butyl-5-nitro-phenol: 1H NMR (400 MHz, DMSO-d6) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitro-phenol: 1H NMR (400 MHz, CDCl3) delta 11.48 (s, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
29%		The mixture of carbonic acid 2,4-di-fer/-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-/er/-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding cone. HC1 and partitioned between water and diethyl ether. The ether layer was dried (MgSCri), concentrated and purified by column chromatography (0 - 5 % ethyl acetate - hexanes) to provide 2,4-di-/er/-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-/c/V-butyl-6-nitro-phenol. 2,4-Di-/er/-butyl-5-nitro-phenol: 1H NMR (400 MHz, DMSO-i) d 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, (0431) 9H). 2,4-Di-/er/-butyl-6-nitro-phenol: NMR (400 MHz, CDCb) d 11.48 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
		The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 12.9 mmol) was dissolved in MeOH (65 mL) and KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding conc. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-5% ethyl acetate-hexanes) to provide 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tent-butyl-5-nitro-phenol: 1H NMR (400 MHz, DMSO-d6) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitro-phenol: 1H NMR (400 MHz, CDCl3) delta 11.48 (s, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H)
		To a stirring mixture of carbonic acid 2,4-di-tert-butyl-phenyl ester methyl ester (4.76 g, 180 mmol) in cone, sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50 C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgSO4) concentrated and purified by column chromatography (0 - 10% ethyl acetate - hexanes) to yield a mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step. The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding cone. HC1 and partitioned between water and diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0 - 5 % ethyl acetate - hexanes) to provide 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Oi-tert-butyl-5-nitro-phenol: 1H NMR (400 MHz, DMSO-d6) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitro-phenol: 1H NMR (400 MHz, CDCl3) delta 11.48 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
		To a stirring mixture of carbonic acid 2,4-di-tert-butyl-phenyl ester methyl ester (4.76 g, 180 mmol) in conc. sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50 ^C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0- 10% ethyl acetate - hexanes) to yield a mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step. The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding conc. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by columnchromatography (0- 5 % ethyl acetate- hexanes) to provide 2,4-di-tert-butyl-5-nitro- phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tert- butyl-5-nitro-phenol:1H NMR (400 MHz, DMSO-d6) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitro-phenol:1H NMR (400 MHz, CDCl3) delta 11.48 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
1.31 g		To a stirring mixture of carbonic acid 2,4-di-tert-butyl-phenyl ester methyl ester (4.76 g, 180 mmol) in conc. sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50 C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-10% ethyl acetate hexanes) to yield a mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step. Step C: 2,4-Di-tert-butyl-5-nitro-phenol and 2,4-Di-tert-butyl-6-nitro-phenol (0101) The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in 50 MeOH (65 mL) before 51 KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding cone. HCl and partitioned between water and diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-5% ethyl acetate-hexanes) to provide 52 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tert-butyl-5-nitro-phenol: 1H NMR (400 MHz, DMSO-d6) delta 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H) ppm. 2,4-Di-tert-butyl-6-nitro-phenol: 1H NMR (400 MHz, CDCl3) delta 11.48 (s, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H) ppm.
1.31 g		1003371 To a stirring mixture of carbonic acid 2,4-di-tert-butyl-phenyl ester methyl ester (4.76 g, 180 mmol) in conc. sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50 C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0 - 10% ethyl acetate - hexanes) to yield a mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and Ccarbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step.; The mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding conc. HC1 and partitioned between water and diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0 - 5 % ethyl acetate - hexanes) to provide 2,4-di-tert-butyl-5-nitro-phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6-nitro-phenol. 2,4-Di-tert-butyl-5 -nitro-phenol: ?H NMR (400 IVIHz, DMSO-d6) 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6-nitro-phenol: ?H NMR (400 IVIFIz, CDC13) 11.48 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
1.31 g		To a stirring mixture of carbonic acid 2,4-di -//77-butyl -phenyl ester methyl ester (4.76 g, 180 mmol) in cone sulfuric acid (2 mL), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mL) and nitric acid (2 mL). The addition was done slowly so that the reaction temperature did not exceed 50 C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgS04), concentrated and purified by column chromatography (0 - 10% ethyl acetate - hexanes) to yield a mixture of carbonic acid 2,4-di-/er/-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-/er/-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step.; The mixture of carbonic acid 2,4-di-ie/t-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-/er/-butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mL) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding cone. HC1 and partitioned between water and diethyl ether. (0821) The ether layer was dried (MgS04), concentrated and purified by column (0822) chromatography (0 - 5 % ethyl acetate - hexanes) to provide 2, 4-di -//77-butyl -5-nitro- phenol (1.31 g, 29% over 2 steps) and 2,4-di-ie/7-butyl-6-nitro-phenol. 2,4-Di-ie/T-butyl- 5-nitro-phenol: 1H NMR (400 MHz, DMSO-zfc) d 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-ferf-butyl-6-nitro-phenol: 1H NMR (400 MHz, CDCb) d 11.48 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 1.47 (s, 9H), 1.34 (s, 9H).
		To a stirring mixture of carbonic acid 2,4-di-tert- butyl-phenyl ester methyl ester (4.76 g, 180 mmol) in conc. sulfuric acid (2 mE), cooled in an ice-water bath, was added a cooled mixture of sulfuric acid (2 mE) and nitric acid (2 mE). The addition was done slowly so that the reaction temperature did not exceed 50 C. The reaction was allowed to stir for 2 h while warming to room temperature. The reaction mixture was then added to ice-water and extracted into diethyl ether. The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-10% ethyl acetate-hexanes) to yield a mixture of carbonic acid 2,4-di-tert-butyl-5-nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert-butyl-6-nitro-phenyl ester methyl ester as a pale yellow solid (4.28 g), which was used directly in the next step.; The mixture of carbonic acid 2,4-di-tert-butyl-5- nitro-phenyl ester methyl ester and carbonic acid 2,4-di-tert- butyl-6-nitro-phenyl ester methyl ester (4.2 g, 14.0 mmol) was dissolved in MeOH (65 mE) before KOH (2.0 g, 36 mmol) was added. The mixture was stirred at room temperature for 2 h. The reaction mixture was then made acidic (pH 2-3) by adding conc. HC1 and partitioned between water and diethyl ethet The ether layer was dried (MgSO4), concentrated and purified by column chromatography (0-5% ethyl acetate-hexanes) to provide 2,4-di-tert-butyl-5-nitro- phenol (1.31 g, 29% over 2 steps) and 2,4-di-tert-butyl-6- nitro-phenol. 2,4-Di-tert-butyl-5-nitro-phenol: ?H NMR (400 MHz, DMSO-d6) oe 10.14 (s, 1H, OH), 7.34 (s, 1H), 6.83 (s, 1H), 1.36 (s, 9H), 1.30 (s, 9H). 2,4-Di-tert-butyl-6- nitro-phenol: ?H NMR (400 MHz, CDC13) oe 11.48 (s, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 1.47 (s, 9H),1.34 (s, 9H).

Reference： [1]Chemistry - A European Journal,2019,vol. 25,p. 3662 - 3674
[2]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 0514; 0515
[3]Patent: WO2019/18395,2019,A1 .Location in patent: Paragraph 00181
[4]Patent: WO2019/18353,2019,A1 .Location in patent: Paragraph 00150
[5]Patent: WO2018/227049,2018,A1 .Location in patent: Paragraph 00208; 00211-00214
[6]Patent: WO2019/191620,2019,A1 .Location in patent: Paragraph 00428-00429
[7]Patent: US2019/240197,2019,A1 .Location in patent: Paragraph 0575; 0577; 0578
[8]Patent: WO2020/102346,2020,A1 .Location in patent: Paragraph 00119; 00120
[9]Patent: US2010/168094,2010,A1 .Location in patent: Page/Page column 72; 73
[10]Patent: WO2018/64632,2018,A1 .Location in patent: Paragraph 00217; 00221; 00222; 00223
[11]Patent: WO2018/107100,2018,A1 .Location in patent: Paragraph 00236; 00239; 00240
[12]Patent: US2018/280349,2018,A1 .Location in patent: Paragraph 0098; 0100-0101
[13]Patent: WO2019/10092,2019,A1 .Location in patent: Paragraph 00324; 00325; 00333; 00336; 00337; 00338; 00339
[14]Patent: WO2019/113089,2019,A1 .Location in patent: Paragraph 00247; 00248
[15]Patent: US2019/119253,2019,A1 .Location in patent: Paragraph 0516; 0518; 0519

5
[ 873055-54-0 ]
[ 873055-57-3 ]

Reference： [1]Patent: US2011/98311,2011,A1
[2]Patent: US2011/98311,2011,A1
[3]Journal of Medicinal Chemistry,2014,vol. 57,p. 9776 - 9795

6
[ 96-76-4 ]
[ 873055-57-3 ]

Yield	Reaction Conditions	Operation in experiment
92.3%	With sulfuric acid; nitric acid; In dichloromethane; at 0 - 10℃; for 1h;	Weighed compound 1 (20.6 g, 0.1mol) in 250 mL three-necked flask, 100 mL of dichloromethane was added, Control the temperature at 5 C to 10 C, a 1:1 mixture of 12 mL of concentrated sulfuric acid and concentrated nitric acid was added dropwise. Drop finished, The control temperature was stirred at 0 C-5 C for 1 h. After the reaction is completed, the reaction system is directly added to the ice water, Stirred for 5 minutes, allowed to stand, The aqueous phase was extracted twice with dichloromethane, The combined methylene chloride layer, Washed twice with saturated aqueous sodium chloride solution, Dried over anhydrous sodium sulfate, filtered, The filtrate was concentrated under reduced pressure to give compound 2 in an amount of 23.2 g, yield 92.3%.

Reference： [1]Patent: CN103787968,2016,B .Location in patent: Paragraph 0039; 0044; 0045
[2]Patent: WO2014/118805,2014,A1
[3]Journal of Medicinal Chemistry,2014,vol. 57,p. 9776 - 9795
[4]Patent: US2015/231142,2015,A1
[5]Patent: US2011/98311,2011,A1
[6]Patent: US2011/98311,2011,A1
[7]Patent: US2017/96397,2017,A1
[8]Patent: WO2018/107100,2018,A1
[9]Chemistry - A European Journal,2019,vol. 25,p. 3662 - 3674

7
[ 873055-55-1 ]
[ 873055-57-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In methanol;	In a clean round bottom flask charge, 2,4-di-tert-butyl-5-nitrophenyl methyl carbonate (10.0 gm) and potassium hydroxide ( 2.71 gm) in 60.0 ml of methanol. The reaction mass was stirred for 2- 3 hr and concentrated. To the residue water and ethyl acetate was added and pH was adjusted to 1.0 to 3.0 by con HC1. The organic layer was washed with 10 % sodium chloride solution and then concentrated ethyl acetate toe get solid. The solid was dissolved in 50.0 ml of methanol and charge 10 % palladium carbon (0.37 gm) in hydrogenater. To this a 5.0 to 6.0 kg Hydrogen pressure was applied and maintained for 2.0 hr at 25- 30. The reaction mass was filtered and 50.0 ml water was added and maintained for 2.0 hr at 25-30 C. The reaction mass was filtered and purified with 40.0 ml of n-hexane to get 6.0 gm of title product. Chromatographic purity by HPLC 99.98 %

Reference： [1]Patent: WO2014/118805,2014,A1 .Location in patent: Paragraph 0287
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 9776 - 9795

8
[ 873055-57-3 ]
[ 873054-44-5 ]

Reference： [1]Patent: WO2014/118805,2014,A1
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 9776 - 9795
[3]Patent: WO2007/79139,2007,A2
[4]Patent: CN103787968,2016,B
[5]Patent: WO2017/37672,2017,A1
[6]Patent: WO2017/37672,2017,A1
[7]Patent: WO2018/64632,2018,A1
[8]Patent: US2017/96397,2017,A1
[9]Patent: WO2018/107100,2018,A1
[10]Patent: US2018/280349,2018,A1
[11]Patent: WO2019/18353,2019,A1
[12]Patent: US2019/119253,2019,A1
[13]Patent: WO2019/113089,2019,A1
[14]Patent: WO2018/227049,2018,A1
[15]Patent: US2019/240197,2019,A1
[16]Patent: WO2019/191620,2019,A1

9
[ 873055-57-3 ]
[ 1085-21-8 ]

Reference： [1]Patent: US2015/231142,2015,A1

10
[ 873055-57-3 ]
C₂₁H₂₉NO [ No CAS ]

Reference： [1]Patent: CN103787968,2016,B

11
[ 873055-57-3 ]
C₃₁H₃₄N₂O₃ [ No CAS ]

Reference： [1]Patent: CN103787968,2016,B

12
[ 873055-57-3 ]
[ 100-44-7 ]
C₂₁H₂₇NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82.9%	With triethylamine; In dichloromethane; at 0 - 20℃; for 2h;	At 10 ~ 20 C, Weighed compound 2 (25.1g, 0.1mol) in 250 mL three-necked flask, 100 mL of dichloromethane was added, Triethylamine (10.1g, 0.1mol), Then drop the temperature to 0-10 C, BnCl (13.3 g, 0.105 mol) was added dropwise, After dropping stirred at room temperature for 2 h, After completion of the reaction, 50 ml of water was added, The phases were separated and the aqueous phase was extracted twice with dichloromethane, The combined methylene chloride layers were washed twice with saturated aqueous sodium chloride solution, Dried over anhydrous sodium sulfate, filtered, The filtrate was concentrated under reduced pressure to give compound 3 in an amount of 28.3 g, yield 82.9%.

Reference： [1]Patent: CN103787968,2016,B .Location in patent: Paragraph 0039; 0054; 0055

13
[ 873055-57-3 ]
2,4-di-tert-butyl-5-(3-(2-fluorophenyl)-3-oxopropanamido)phenyl methyl carbonate [ No CAS ]

Reference： [1]Patent: WO2017/37672,2017,A1

14
[ 873055-57-3 ]
2,4-di-tert-butyl-5-(3-ethoxy-2-(2-fluorobenzoyl)acrylamido)phenyl methyl carbonate [ No CAS ]

Reference： [1]Patent: WO2017/37672,2017,A1
[2]Patent: WO2017/37672,2017,A1

15
[ 873055-57-3 ]
[ 1182822-31-6 ]

Reference： [1]Patent: WO2017/37672,2017,A1
[2]Patent: US2017/96397,2017,A1

16
[ 873055-57-3 ]
5-([(E)-3-ethoxyprop-2-enoyl]amino)-2,4-di-tert-butylphenyl methyl carbonate [ No CAS ]

Reference： [1]Patent: WO2017/37672,2017,A1

17
[ 873055-57-3 ]
[ 79-22-1 ]
[ 873055-55-1 ]

Yield	Reaction Conditions	Operation in experiment
36.6 g	With dmap; triethylamine; In dichloromethane; at 0 - 30℃;	Example-17: Preparation of compound of Formula IVp. 2,4-di-feri-butyl-5-nitro phenol (30g), N,N-dimethylamino pyridine (0.73g), triethylamine (24.16 g) and methylene chloride ( 120mL) were charged in to round bottom flask at 25- 35C. Reaction mass was cooled to 0-5C, methyl chloro formate (16.92g) was slowly added over a period of 60 min and reaction mass was heated to 25-30C. After completion of the reaction, filtered the reaction mass and washed with ethyl acetate (150mL). Combined organic layer distilled completely under vacuum at below 40C. Then the resultant crude mass was dissolved in to ethyl acetate (3000mL) and washed with water (150mL) and 5% aqueous hydrochloride solution (150mL) and followed by water ( 150mL). Organic layer was distilled completely to get 2,4-di feri-butyl-5-nitro phenyl methyl carbonate (36.6g). To the obtained 2,4-di-feri-butyl-5-nitro phenyl methyl carbonate (22.5g) was added aqueous ammonium chloride (38.90g), ethanol (225), Iron (16.23g) at room temperature and heated to reflux for 3 hrs. After completion of the reaction, temperature was cooled to 30C and filtered through celite. The celite was washed with ethanol and combined filtrates were distilled completely under vacuum at below 50C. To the obtained reaction mass water (1 12mL) was added at 25-35 C and stirred for 30 min and filtered the precipitated solid and washed with water (60mL) to get 5-amino-2,4-di-feri-butyl phenyl methyl carbonate of Formula IVp as a white solid (18.75g).

Reference： [1]Patent: WO2017/37672,2017,A1 .Location in patent: Page/Page column 51

18
2,4-di-tert-butylphenyl ethyl carbonate [ No CAS ]
[ 873055-57-3 ]

Yield	Reaction Conditions	Operation in experiment
		A clean and dry 5 liter round bottom flask, fitted with mechanical stirrer, thermo pocket and dropping funnel was charged with Methanol (2500 ml) and the mixture of 2, 4 di-tert-butyl-5-nitro phenyl ethyl carbonate and 2, 4 di-tert-butyl-6-nitro phenyl ethyl carbonate (obtained in example-2) at 25-30 C. The reaction mass was cooled to 0-5 C. and Potassium hydroxide (260 g) was added portion-wise while maintaining the internal temperature 0-5 C., The temperature was raised to 25-30 C. and maintained under stirring for 60-90 minutes for completion of the reaction. After completion of the reaction, the reaction mass was cooled to 10-15 C. and the pH was adjusted to 2-3 with dilute hydrochloric acid (-800 ml). The flask was then charged with water (2500 ml) and ethyl acetate (2500 ml) and stirred for 15-20 minutes at 25-30 C. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×1250 ml). All organic layers were combined and washed with water (2500 ml). The ethyl acetate was distilled out under reduced pressure at 45-50 C. to obtain an oily residue. Charged n-hexane (250 ml) and distilled out n-hexane completely to remove traces of ethyl acetate. The reaction mass was cooled to 0-5 C. and maintained under stirring for 90-120 minutes at 0-5 C. The resultant composition was filtered and washed with chilled n-hexane (100 ml). The wet product was dried at 45 C. to to obtain title compound 130-170 grams.

Reference： [1]Patent: US2017/96397,2017,A1 .Location in patent: Paragraph 0086

19
[ 96-76-4 ]
[ 873055-57-3 ]
[ 20039-94-5 ]

Reference： [1]Patent: WO2018/64632,2018,A1
[2]Patent: US2018/280349,2018,A1
[3]Patent: WO2018/227049,2018,A1
[4]Patent: WO2019/10092,2019,A1
[5]Patent: WO2019/18395,2019,A1
[6]Patent: WO2019/18353,2019,A1
[7]Patent: US2019/119253,2019,A1
[8]Patent: WO2019/113089,2019,A1
[9]Patent: US2019/240197,2019,A1
[10]Patent: WO2019/191620,2019,A1
[11]Patent: WO2020/102346,2020,A1

20
[ 873055-57-3 ]
1-benzyl-3-(1-(2,4-di-tert-butyl-5-hydroxyphenyl)-1H-1,2,3-triazol-4-yl)quinolin-4(1H)-one [ No CAS ]

Reference： [1]Chemistry - A European Journal,2019,vol. 25,p. 3662 - 3674

21
[ 873055-57-3 ]
3-(1-(2,4-di-tert-butyl-5-hydroxyphenyl)-1H-1,2,3-triazol-4-yl)quinolin-4(1H)-one [ No CAS ]

Reference： [1]Chemistry - A European Journal,2019,vol. 25,p. 3662 - 3674

22
[ 873055-57-3 ]
5-azido-2,4-di-tertbutylphenol [ No CAS ]

Reference： [1]Chemistry - A European Journal,2019,vol. 25,p. 3662 - 3674

23
[ 873055-57-3 ]
(5-azido-2,4-di-tert-butylphenoxy)trimethylsilane [ No CAS ]

Reference： [1]Chemistry - A European Journal,2019,vol. 25,p. 3662 - 3674

Same Skeleton Products

Related Products

Historical Records

Related Functional Groups of
[ 873055-57-3 ]

Aryls

[ 6683-81-4 ]

2-(tert-Butyl)-4-nitrophenol

Similarity: 0.95

[ 728-40-5 ]

2,6-Di-tert-butyl-4-nitrophenol

Similarity: 0.93

[ 180628-74-4 ]

3-(Hydroxymethyl)-5-nitrophenol

Similarity: 0.88

[ 2423-71-4 ]

2,6-Dimethyl-4-nitrophenol

Similarity: 0.86

[ 5460-31-1 ]

2-Methyl-3-nitrophenol

Similarity: 0.86

Nitroes

[ 6683-81-4 ]

2-(tert-Butyl)-4-nitrophenol

Similarity: 0.95

[ 728-40-5 ]

2,6-Di-tert-butyl-4-nitrophenol

Similarity: 0.93

[ 180628-74-4 ]

3-(Hydroxymethyl)-5-nitrophenol

Similarity: 0.88

[ 2423-71-4 ]

2,6-Dimethyl-4-nitrophenol

Similarity: 0.86

[ 5460-31-1 ]

2-Methyl-3-nitrophenol

Similarity: 0.86

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
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
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. 873055-57-3 ] {[proInfo.proName]}

Quality Control of [ 873055-57-3 ]

Related Doc. of [ 873055-57-3 ]

Product Details of [ 873055-57-3 ]

Safety of [ 873055-57-3 ]

Application In Synthesis of [ 873055-57-3 ]

[ 873055-57-3 ] Synthesis Path-Upstream 1~6

[ 873055-57-3 ] Synthesis Path-Downstream 1~23

Related Functional Groups of [ 873055-57-3 ]

Aryls

Nitroes

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 873055-57-3 ]