[ CAS No. 201932-92-5 ] {[proInfo.proName]}

Name: 201932-92-5|Methyl 3-(hydroxymethyl)-4-nitrobenzoate|97%
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SKU: A147033
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Quality Control of [ 201932-92-5 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 201932-92-5 ]

SDS Specification

Alternatived Products of [ 201932-92-5 ]

Product Details of [ 201932-92-5 ]

CAS No. :	201932-92-5	MDL No. :	MFCD29762434
Formula :	C₉H₉NO₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UZYJUGUGWPESHO-UHFFFAOYSA-N
M.W :	211.17	Pubchem ID :	18372008
Synonyms :

Calculated chemistry of [ 201932-92-5 ]

Physicochemical Properties

Num. heavy atoms :	15
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	4
Num. H-bond acceptors :	5.0
Num. H-bond donors :	1.0
Molar Refractivity :	52.67
TPSA :	92.35 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.08 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.48
Log Po/w (XLOGP3) :	0.72
Log Po/w (WLOGP) :	0.72
Log Po/w (MLOGP) :	0.34
Log Po/w (SILICOS-IT) :	-0.55
Consensus Log Po/w :	0.54

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.63
Solubility :	4.9 mg/ml ; 0.0232 mol/l
Class :	Very soluble
Log S (Ali) :	-2.24
Solubility :	1.22 mg/ml ; 0.00579 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.69
Solubility :	4.3 mg/ml ; 0.0204 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.05

Safety of [ 201932-92-5 ]

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

Application In Synthesis of [ 201932-92-5 ]

* 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 [ 201932-92-5 ]
Downstream synthetic route of [ 201932-92-5 ]

[ 201932-92-5 ] Synthesis Path-Upstream 1~4

1
[ 201932-92-5 ]
[ 79-37-8 ]
[ 148625-35-8 ]

Reference： [1] Patent: US6500405, 2002, B1,
[2] Patent: US5874466, 1999, A,
[3] Patent: US5929098, 1999, A,
[4] Patent: US5981435, 1999, A,
[5] Patent: EP816328, 1998, A2,
[6] Patent: EP878192, 1998, A2,
[7] Patent: EP880893, 1998, A1,
[8] Patent: EP834311, 1998, A1,

2
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[ 148625-35-8 ]

Reference： [1] Patent: WO2007/87129, 2007, A2, . Location in patent: Page/Page column 67

3
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[ 201932-92-5 ]

Yield	Reaction Conditions	Operation in experiment
1.06 g	at 0℃; for 0.333333 h;	( RS-3-49) Methyl 3-formyl-4-nitrobenzoate (1.20 g, 5.73 mmol) was dissolved in MeOH (10 mL) and cooled to 0 °C. Sodium borohydride (69 mg, 1.72 mmol) was added in one portion, and the reaction mixture was stirred for 20 minutes. The reduction was quenched with 1 N HC1 (10 mL) and the methanol portion evaporated in vacuo. The aqueous phase was extracted with CH₂C1₂ (3 ^χ 10 mL) to afford 1.06 g of benzylic alcohol, which was used without further purification .

Reference： [1] Patent: WO2014/131023, 2014, A1, . Location in patent: Page/Page column 138
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 10, p. 4812 - 4830

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Reference： [1] Patent: WO2007/87129, 2007, A2, . Location in patent: Page/Page column 67

[ 201932-92-5 ] Synthesis Path-Downstream 1~15

1
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[ 4637-24-5 ]
[ 201932-92-5 ]

Yield	Reaction Conditions	Operation in experiment
	at 140℃; for 22.5h;	A solution of <strong>[24078-21-5]3-methyl-4-nitro-benzoic acid methyl ester</strong> (24.99 g, 128.1 mmol) and N,N-dimethylformamide dimethyl acetal (40.0 mL, 300 mmol) was heated at 1400C for 22.5 h. After cooling to rt, the reaction mixture was concentrated and the residue was crystallized from MeOH to give a purple solid.This solid was dissolved in THF (500 mL) and water (500 mL), and sodium periodate (62.62 g, 292.8 mmol) was added followed by additional sodium periodate (15.6 g, 72.9 mmol) two hours later. After stirring at rt for an additional 1 h, the reaction mixture was filtered through Celite washing with EtOAc (2 L). The filtrate was washed with saturated NaHCO3 (600 mL) and the organic layer was dried over Na2SO4. After filtration, the filtrate was concentrated and the residue was passed through a pad of silica gel, washing with CH2Cl2/hexanes (75%- 100%). The filtrate was concentrated and dried to give 3-formyl-4-nitro-benzoic acid methyl ester as yellowish solid. MS (EI): cal'd 210.0 (MH+), exp 210.2 (MH+).

Reference： [1]Patent: WO2007/87129,2007,A2 .Location in patent: Page/Page column 67

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[ 148625-35-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium periodate; In tetrahydrofuran; water; at 20℃; for 3h;	A solution of 3-methyl-4-nitro-benzoic acid methyl ester (24.99 g, 128.1 mmol) and N,N-dimethylformamide dimethyl acetal (40.0 mL, 300 mmol) was heated at 1400C for 22.5 h. After cooling to rt, the reaction mixture was concentrated and the residue was crystallized from MeOH to give a purple solid.This solid was dissolved in THF (500 mL) and water (500 mL), and sodium periodate (62.62 g, 292.8 mmol) was added followed by additional sodium periodate (15.6 g, 72.9 mmol) two hours later. After stirring at rt for an additional 1 h, the reaction mixture was filtered through Celite washing with EtOAc (2 L). The filtrate was washed with saturated NaHCO3 (600 mL) and the organic layer was dried over Na2SO4. After filtration, the filtrate was concentrated and the residue was passed through a pad of silica gel, washing with CH2Cl2/hexanes (75percent- 100percent). The filtrate was concentrated and dried to give 3-formyl-4-nitro-benzoic acid methyl ester as yellowish solid. MS (EI): cal'd 210.0 (MH+), exp 210.2 (MH+).

Reference： [1]Patent: WO2007/87129,2007,A2 .Location in patent: Page/Page column 67

Yield	Reaction Conditions	Operation in experiment
		d) Preparation of methyl 3-hydroxymethyl-4-nitrobenzoate In a 5-liter three-necked round-bottomed flask equipped with a reflux condenser, overhead stirrer and nitrogen inlet, was placed 318 g of the previously prepared methyl 3-acetoxymethyl-4-nitrobenzoate and 3.2 l of anhydrous methanol. To the resulting solution was bubbled in 40 g of hydrogen chloride and the resulting mixture was refluxed for 3 hours. After cooling to room temperature the solvent was removed using a rotary evaporator yielding 273 g of methyl 3-hydroxymethyl-4-nitrobenzoate as a yellow solid containing traces of methanol, which was used as such in the next step.
		d) Preparation of methyl 3-hydroxymethyl-4-nitrobenzoate. In a 5-liter three-necked round-bottomed flask equipped with a reflux condenser, overhead stirrer and nitrogen inlet, was placed 318 g of the previously prepared methyl 3-acetoxymethyl-4-nitrobenzoate and 3.21 of anhydrous methanol. To the resulting solution was bubbled in 40 g of hydrogen chloride and the resulting mixture was refluxed for 3 hours. After cooling to room temperature the solvent was removed using rotary evaporator yielding 273 g of methyl 3-hydroxymethyl-4-nitrobenzoate as a yellow solid containing traces of methanol, which was used as such in the next step.
		d) Preparation of methyl 3-hydroxymethyl-4-nitrobenzoate In a 5-liter three-necked round-bottomed flask equipped with a reflux condenser, overhead stirrer and nitrogen inlet, was placed 318 g of the previously prepared methyl 3-acetoxymethyl-4-nitrobenzoate and 3.2 l of anhydrous methanol. To the resulting solution was bubbled in 40 g of hydrogen chloride and the resulting mixture was refluxed for 3 hours. After cooling to room temperature the solvent was removed using a rotary evaporator yielding 273 g of methyl 3-hydroxymethyl-4-nitrobenzoate as a yellow solid containing traces of methanol, which was used as such in the next step.

		d) Preparation of methyl 3-hydroxymethyl-4-nitrobenzoate. In a 5-liter three-necked round-bottomed flask equipped with a reflux condenser, overhead stirrer and nitrogen inlet, was placed 318 g of the previously prepared methyl 3-acetoxymethyl-4-nitrobenzoate and 3.2 l of anhydrous methanol. To the resulting solution was bubbled in 40 g of hydrogen chloride and the resulting mixture was refluxed for 3 hours. After cooling to room temperature the solvent was removed using a rotary evaporator yielding 273 g of methyl 3-hydroxymethyl-4-nitrobenzoate as a yellow solid containing traces of methanol, which was used as such in the next step.
		d) Preparation of methyl 3-hydroxymethyl-4-nitrobenzoate. In a 5-liter three-necked round-bottomed flask equipped with a reflux condenser, overhead stirrer and nitrogen inlet, was placed 318 g of the previously prepared methyl 3-acetoxymethyl-4-nitrobenzoate and 3.2 l of anhydrous methanol. To the resulting solution was bubbled in 40 g of hydrogen chloride and the resulting mixture was refluxed for 3 hours. After cooling to room temperature the solvent was removed using a rotary evaporator yielding 273 g of methyl 3-hydroxymethyl-4-nitrobenzoate as a yellow solid containing traces of methanol, which was used as such in the next step.
		d) Preparation of methyl 3-hydroxymethyl-4-nitrobenzoate. In a 5-liter three-necked round-bottomed flask equipped with a reflux condenser, overhead stirrer and nitrogen inlet, was placed 318 g of the previously prepared methyl 3-acetoxymethyl-4-nitrobenzoate and 3.2 1 of anhydrous methanol. To the resulting solution was bubbled in 40 g of hydrogen chloride and the resulting mixture was refluxed for 3 hours. After cooling to room temperature the solvent was removed using a rotary evaporator yielding 273 g of methyl 3-hydroxymethyl-4-nitrobenzoate as a yellow solid containing traces of methanol, which was used as such in the next step.
		d) Preparation of methyl 3-hydroxymethyl-4-nitrobenzoate. In a 5-liter three-necked round-bottomed flask equipped with a reflux condenser, overhead stirrer and nitrogen inlet, was placed 318 g of the previously prepared methyl 3-acetoxymethyl-4-nitrobenzoate and 3.2 l of anhydrous methanol. To the resulting solution was bubbled in 40 g of hydrogen chloride and the resulting mixture was refluxed for 3 hours. After cooling to room temperature the solvent was removed using a rotary evaporator yielding 273 g of methyl 3-hydroxymethyl-4-nitrobenzoate as a yellow solid containing traces of methanol, which was used as such in the next step.
		d) Preparation of methyl 3-hydroxymethyl-4-nitrobenzoate. In a 5-liter three-necked round-bottomed flask equipped with a reflux condenser, overhead stirrer and nitrogen inlet, was placed 318 g of the previously prepared methyl 3-acetoxymethyl-4-nitrobenzoate and 3.2 1 of anhydrous methanol. To the resulting solution was bubbled in 40 g of hydrogen chloride and the resulting mixture was refluxed for 3 hours. After cooling to room temperature the solvent was removed using a rotary evaporator yielding 273 g of methyl 3 -hydroxymethyl-4-nitrobenzoate as a yellow solid containing traces of methanol, which was used as such in the next step.

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[ 79-37-8 ]
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Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate;	e) Preparation of methyl 3-formyl-4-nitrobenzoate In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78° C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70° C. After the addition was complete the reaction mixture was stirred at -78° C. for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65° C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2250 mL), water (2250 mL), saturated aqueous sodium bicarbonate (2250 mL), water (2200 mL), brine (1*200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid.
	With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate;	e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78° C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70° C. After the addition was complete the reaction mixture was stirred at -78° C. for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65° C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2250 mL), water (2250 mL), saturated aqueous sodium bicarbonate (2250 mL), water (2200 mL), brine (1*200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid.
	With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate;	e) Preparation of methyl 3-formyl-4-nitrobenzoate In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78° C. Oxalyl chloride (164 g 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70° C. After the addition was complete the reaction mixture was stirred at -78° C. for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65° C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2250 mL), water (2250 mL), saturated aqueous sodium bicarbonate (2250 mL), water (2200 mL), brine (1*200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid.

	With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate;	e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78° C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70° C. After the addition was complete the reaction mixture was stirred at -78° C. for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65° C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2250 mL), water (2250 mL), saturated aqueous sodium bicarbonate (2250 mL), water (2200 mL), brine (1*200 mL) and dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid.
	With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate;	e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78 oC. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70 oC. After the addition was complete the reaction mixture was stirred at -78 oC for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65 oC. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2x250 mL), water (2x250 mL), saturated aqueous sodium bicarbonate (2x250 mL), water (2x200 mL), brine (1x200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid.
	With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate;	e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78 °C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70 °C. After the addition was complete the reaction mixture was stirred at -78 °C for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65 °C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2x250 mL), water (2x250 mL), saturated aqueous sodium bicarbonate (2x250 mL), water (2x200 mL), brine (1x200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid.
	With triethylamine; In dichloromethane; water; dimethyl sulfoxide;	e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78 °C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70 °C. After the addition was complete the reaction mixture was stirred at -78 °C for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65 °C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 1 of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2x250 mL), water (2x250 mL), saturated aqueous sodium bicarbonate (2x250 mL), water (2x200 mL), brine (1x200 mL) and dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid.
	With triethylamine; In dichloromethane; dimethyl sulfoxide;	e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 1 of methylene chloride was cooled to -78°C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70°C. After the addition was complete the reaction mixture was stirred at -78 °C for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65 °C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 1 of ethyl acetate and 11 of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2x250 mL), water (2x250 mL), saturated aqueous sodium bicarbonate (2x250 mL), water (2x200 mL), brine (1x200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid.

Reference： [1]Patent: US6500405,2002,B1
[2]Patent: US5874466,1999,A
[3]Patent: US5929098,1999,A
[4]Patent: US5981435,1999,A
[5]Patent: EP816328,1998,A2
[6]Patent: EP878192,1998,A2
[7]Patent: EP880893,1998,A1
[8]Patent: EP834311,1998,A1

5
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[ 201932-92-5 ]

Yield	Reaction Conditions	Operation in experiment
1.06 g	With methanol; sodium tetrahydroborate; at 0℃; for 0.333333h;	( RS-3-49) Methyl 3-formyl-4-nitrobenzoate (1.20 g, 5.73 mmol) was dissolved in MeOH (10 mL) and cooled to 0 °C. Sodium borohydride (69 mg, 1.72 mmol) was added in one portion, and the reaction mixture was stirred for 20 minutes. The reduction was quenched with 1 N HC1 (10 mL) and the methanol portion evaporated in vacuo. The aqueous phase was extracted with CH2C12 (3 chi 10 mL) to afford 1.06 g of benzylic alcohol, which was used without further purification .

Reference： [1]Patent: WO2014/131023,2014,A1 .Location in patent: Page/Page column 138
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 4812 - 4830

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[ 88071-90-3 ]

Yield	Reaction Conditions	Operation in experiment
30%	With phosphorus tribromide; In diethyl ether; for 1.0h;	( RS-3-53) Benzylic alcohol MRS-3-49 (1.06 g, 5.35 mmol) was dissolved in Et20 (15 mL) and cooled to 0 C. Phosphorus tribromide (0.254 mL, 2.67 mmol) was carefully added dropwise. After 1 hour, the reaction mixture was poured into ice water (50 mL) and extracted with Et20 (3 chi 20 mL) . The ethereal phases were washed with sat. NaHC03 (20 mL) , water (10 mL) and sat. aqueous NaCl (10 mL) , and dried over Na2S04. Evaporation of the Et20 revealed 440 mg (30%) of the primary alkyl bromide.

Reference： [1]Patent: WO2014/131023,2014,A1 .Location in patent: Page/Page column 138
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 4812 - 4830

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methyl 4-nitro-3-((4-((triisopropylsilyl)oxy)phenoxy)methyl)benzoate [ No CAS ]