[ CAS No. 38170-02-4 ] {[proInfo.proName]}

Name: 38170-02-4|2-Hydroxy-4-iodobenzaldehyde|95%
Brand: Ambeed
SKU: A593317
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Quality Control of [ 38170-02-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 38170-02-4 ]

SDS Specification

Alternatived Products of [ 38170-02-4 ]

Product Details of [ 38170-02-4 ]

CAS No. :	38170-02-4	MDL No. :	MFCD08457196
Formula :	C₇H₅IO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UPUMRAVJDXWXMP-UHFFFAOYSA-N
M.W :	248.02	Pubchem ID :	18351513
Synonyms :

Calculated chemistry of [ 38170-02-4 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	46.57
TPSA :	37.3 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.23 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.34
Log Po/w (XLOGP3) :	2.23
Log Po/w (WLOGP) :	1.81
Log Po/w (MLOGP) :	1.71
Log Po/w (SILICOS-IT) :	2.47
Consensus Log Po/w :	1.91

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.16
Solubility :	0.171 mg/ml ; 0.000691 mol/l
Class :	Soluble
Log S (Ali) :	-2.65
Solubility :	0.557 mg/ml ; 0.00225 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.73
Solubility :	0.465 mg/ml ; 0.00187 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.65

Safety of [ 38170-02-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 38170-02-4 ]

* 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 [ 38170-02-4 ]
Downstream synthetic route of [ 38170-02-4 ]

[ 38170-02-4 ] Synthesis Path-Upstream 1~11

1
[ 50-00-0 ]
[ 533-58-4 ]
[ 38170-02-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine; magnesium chloride In acetonitrile at 10 - 72℃; for 2 h;	4-(nitrooxy)butyl (2R)-7-benzyl-6-chloro-2-(trifluoromethyl)-2H-chromene-3- carboxylate; Step 1; Preparation of 2-hydroxy-4-iodobenzaldehyde; [0168] To a chilled solution of commercially available 2-iodophenol (30 g, 136 mmole) in ACN was added MgCl₂ (19.5 g, 204 mmole) portion-wise while maintaining the temperature below 10 ⁰C, followed by paraformaldehyde (28.6 g, 954 mmole) and TEA (76 mL, 545 mmole) producing a 15 °C exotherm. The solution was heated to 72 ⁰C for 2 h. The reaction was cooled to room temperature and poured into Saturated aqueous Ammonium Chloride (500 mL), extracted with ethyl acetate (2 X 150 mL). The combined organic phases were washed with aqueous NaHCO₃ solution (2 X 150 mL), aqueous IN HCl solution (2 X 150 mL), and brine (2 X 150 mL), dried over Na₂SO₄, filtered and concentrated in vacuo. The crude material was subjected to flash chromatography (Silica, 5percent Ethyl acetate/ Hexane). Desired fractions were collected and combined, removed solvent in vacuo producing the ethyl ester (27 g, 79percent) as a yellow solid. This salicylaldehyde was of suitable purity to use without further purification.
79%	With triethylamine; magnesium chloride In acetonitrile at 10 - 72℃; for 2 h;	[0232] To a chilled solution of commercially available 2-iodophenol (30 g, 136 mmole) in ACN was added MgCl2 (19.5 g, 204 mmole) portion-wise while maintaining the temperature below 10 °C, followed by PARAFORMALDEHYDE (28.6 g, 954 mmole) and TEA (76 mL, 545 mmole) producing a 15 °C exotherm. The solution was heated to 72 °C for 2 h. The reaction was cooled to room temperature and poured into Saturated aqueous Ammonium Chloride (500 mL), extracted with ethyl acetate (2 X 150 mL). The combined organic phases were washed with aqueous NAHC03 solution (2 X 150 mL), aqueous 1N HCL solution (2 X 150 mL), and brine (2 X 150 mL), dried OVER NA2S04, filtered and concentrated in vacuo. The crude material was subjected to flash chromatography (Silica, 5percent Ethyl ACETATE/HEXANE). Desired fractions were collected and combined, removed solvent in vacuo producing the ethyl ester (27 g, 79percent) as a yellow solid. This salicylaldehyde was of suitable purity to use without FURTHER PURIFICATION. HNMR (DMSO-D6/400 MHz) 10.95 (s, 1H), 10.19 (s, 1H), 7.33 (m, 3H), 4.31 (m, 1H).
79%	With triethylamine; magnesium chloride In acetonitrile at 10 - 72℃; for 2 h;	EXAMPLE 14; (2R)-6-chIoro-5-(3,3-dimethylbutyl)-2-(trifluoromethyl)-l,7b- dihydrocyclopropa[c]chromene-la(2H)-carboxylic acid; Step 1. Preparation of 2-hydroxy-4-iodobenzaldehyde.; [0185] To a chilled solution of commercially available 2-iodophenol (30 g, 136 mmole) in ACN was added MgCl₂ (19.5 g, 204 mmole) portion-wise while maintaining the temperature below 10 ⁰C, followed by paraformaldehyde (28.6 g, 954 mmole) and TEA (76 niL, 545 mmole) producing a 15 °C exotherm. The solution was heated to 72 ⁰C for 2 h. The reaction was cooled to room temperature and poured into Saturated aqueous Ammonium Chloride (500 mL), extracted with ethyl acetate (2 X 150 niL). The combined organic phases were washed with aqueous NaHCO₃ solution (2 X 150 mL), aqueous IN HCl solution (2 X 150 mL), and brine (2 X 150 mL), dried over Na₂SO₄, filtered and concentrated in vacuo. The crude material was subjected to flash chromatography (Silica, 5percent Ethyl acetate/ Hexane). Desired fractions were collected and combined, removed solvent in vacuo producing the ethyl ester (27 g, 79percent) as a yellow solid. This salicylaldehyde was of suitable purity to use without further purification. ¹HNMR (DMSO-J₆/400 MHz) 10.95 (s, IH), 10.19 (s, IH), 7.33 (m, 3H), 4.31 (m, IH).

Reference： [1] Patent: WO2006/40676, 2006, A1, . Location in patent: Page/Page column 51
[2] Patent: WO2004/87686, 2004, A2, . Location in patent: Page 12-130
[3] Patent: WO2004/87687, 2004, A1, . Location in patent: Page 12-130
[4] Patent: WO2006/40672, 2006, A1, . Location in patent: Page/Page column 59

2
[ 50-00-0 ]
[ 626-02-8 ]
[ 38170-02-4 ]

Yield	Reaction Conditions	Operation in experiment
50%	With triethylamine; magnesium chloride In acetonitrileCooling with ice	10 g (45 mmol) of 3-iodobenzoic acid was dissolved in 160 ml of anhydrous acetonitrile, 12.8 g (134 mmol) of anhydrous magnesium chloride was added thereto in portions under ice-cooling, followed by addition of 25.3 ml of triethylamine, (636 mmol) of paraformaldehyde was added in batches, and the reaction was quenched by adding 1 M HC1 to adjust the pH to 5. After the reaction, the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and the solvent was passed through 100- 200 mesh silica gel column chromatography, eluting with petroleum ether to give 15.6 g of intermediate, 50percent yield
36%	With triethylamine; magnesium chloride In acetonitrileReflux; Inert atmosphere	To a dry CH₃CN solution (10 mL) of the 1.1 g phenol (5 mmol), anhydrous magnesium chloride (1.42 g, 15 mmol), triethylamine (5.5 mL, 40 mmol) and paraformaldehyde (2.1 g, 70 mmol) were added. The reaction mixture was heated to reflux under an argon atmosphere for overnight and monitored by TLC. Upon cooling, the reaction mixture was dilute with diethyl ether (20 mL). The organic layer was washed successively with HCl (1 M, 210 mL) and water (210 mL), and then dried (MgSO₄). The product was puried by column chromatography (PE EA = 50:1) to afford 0.451 g (36percent) 4b’ as white solid.

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 23, p. 7159 - 7163
[2] Journal of Organic Chemistry, 2015, vol. 80, # 9, p. 4306 - 4312
[3] Patent: CN104119690, 2016, B, . Location in patent: Paragraph 0022; 0023; 0024
[4] Canadian Journal of Chemistry, 2008, vol. 86, # 1, p. 50 - 64
[5] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 15, p. 3057 - 3061
[6] Chemistry - A European Journal, 2013, vol. 19, # 17, p. 5375 - 5386
[7] Patent: WO2005/14566, 2005, A1, . Location in patent: Page/Page column 76-77
[8] Patent: WO2008/57336, 2008, A2, . Location in patent: Page/Page column 45-46
[9] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 20, p. 5591 - 5593
[10] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 9, p. 3223 - 3228
[11] Chemical Communications, 2017, vol. 53, # 26, p. 3645 - 3648
[12] New Journal of Chemistry, 2017, vol. 41, # 18, p. 9796 - 9805

3
[ 50-00-0 ]
[ 626-02-8 ]
[ 38169-97-0 ]
[ 38170-02-4 ]

Reference： [1] Patent: WO2010/56788, 2010, A1, . Location in patent: Page/Page column 89-90

4
[ 67-66-3 ]
[ 626-02-8 ]
[ 38170-02-4 ]

Reference： [1] Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 2, p. 417 - 422
[2] Chemical and pharmaceutical bulletin, 1963, vol. 11, p. 123 - 126

5
[ 18179-39-0 ]
[ 38170-02-4 ]

Reference： [1] Journal of Pharmacy and Pharmacology, 2016, vol. 68, # 2, p. 233 - 244

6
[ 166386-81-8 ]
[ 38170-02-4 ]

Reference： [1] Journal of Pharmacy and Pharmacology, 2016, vol. 68, # 2, p. 233 - 244

7
[ 67-66-3 ]
[ 626-02-8 ]
[ 38170-02-4 ]
[ 90151-01-2 ]

Reference： [1] Journal of the Chemical Society, 1929, p. 469,470
[2] Journal of the Chemical Society, 1927, p. 3043

8
[ 75-25-2 ]
[ 626-02-8 ]
[ 38170-02-4 ]
[ 90151-01-2 ]

Reference： [1] Journal of the Chemical Society, 1929, p. 469,470

9
[ 67-66-3 ]
[ 626-02-8 ]
[ 38170-02-4 ]
[ 90151-01-2 ]

Reference： [1] Journal of the Chemical Society, 1929, p. 469,470
[2] Journal of the Chemical Society, 1927, p. 3043

10
[ 75-25-2 ]
[ 626-02-8 ]
[ 38170-02-4 ]
[ 90151-01-2 ]

Reference： [1] Journal of the Chemical Society, 1929, p. 469,470

11
[ 38170-02-4 ]
[ 21962-45-8 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 9, p. 3223 - 3228

[ 38170-02-4 ] Synthesis Path-Downstream 1~88

1
[ 67-66-3 ]
[ 626-02-8 ]
[ 38170-02-4 ]
[ 90151-01-2 ]

Reference： [1]Journal of the Chemical Society,1929,p. 469,470
[2]Journal of the Chemical Society,1927,p. 3043

2
[ 75-25-2 ]
[ 626-02-8 ]
[ 38170-02-4 ]
[ 90151-01-2 ]

Reference： [1]Journal of the Chemical Society,1929,p. 469,470

3
[ 38170-02-4 ]
[ 856076-61-4 ]
2-hydroxy-4-iodo-3,5-dinitro-benzaldehyde [ No CAS ]

Reference： [1]Journal of the Chemical Society,1928,p. 2276
[2]Journal of the Chemical Society,1928,p. 2276

4
[ 67-66-3 ]
[ 626-02-8 ]
[ 38170-02-4 ]

Reference： [1]Bulletin of the Chemical Society of Japan,2000,vol. 73,p. 417 - 422
[2]Chemical and pharmaceutical bulletin,1963,vol. 11,p. 123 - 126

5
[ 943328-51-6 ]
[ 38170-02-4 ]
C₄₄H₆₂I₂N₂O₄ [ No CAS ]

Reference： [1]Journal of Materials Chemistry,2007,vol. 17,p. 1923 - 1932

6
[ 38170-02-4 ]
2-hydroxy-4-iodo-benzoic acid isopropyl ester [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,2000,vol. 73,p. 417 - 422

7
[ 38170-02-4 ]
[ 89942-34-7 ]

Reference： [1]Chemical and pharmaceutical bulletin,1963,vol. 11,p. 123 - 126

9
[ 50-00-0 ]
[ 533-58-4 ]
[ 38170-02-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine; magnesium chloride; In acetonitrile; at 10 - 72℃; for 2h;	4-(nitrooxy)butyl (2R)-7-benzyl-6-chloro-2-(trifluoromethyl)-2H-chromene-3- carboxylate; Step 1; Preparation of 2-hydroxy-4-iodobenzaldehyde; [0168] To a chilled solution of commercially available 2-iodophenol (30 g, 136 mmole) in ACN was added MgCl2 (19.5 g, 204 mmole) portion-wise while maintaining the temperature below 10 0C, followed by paraformaldehyde (28.6 g, 954 mmole) and TEA (76 mL, 545 mmole) producing a 15 C exotherm. The solution was heated to 72 0C for 2 h. The reaction was cooled to room temperature and poured into Saturated aqueous Ammonium Chloride (500 mL), extracted with ethyl acetate (2 X 150 mL). The combined organic phases were washed with aqueous NaHCO3 solution (2 X 150 mL), aqueous IN HCl solution (2 X 150 mL), and brine (2 X 150 mL), dried over Na2SO4, filtered and concentrated in vacuo. The crude material was subjected to flash chromatography (Silica, 5% Ethyl acetate/ Hexane). Desired fractions were collected and combined, removed solvent in vacuo producing the ethyl ester (27 g, 79%) as a yellow solid. This salicylaldehyde was of suitable purity to use without further purification.
79%	With triethylamine; magnesium chloride; In acetonitrile; at 10 - 72℃; for 2h;	[0232] To a chilled solution of commercially available 2-iodophenol (30 g, 136 mmole) in ACN was added MgCl2 (19.5 g, 204 mmole) portion-wise while maintaining the temperature below 10 C, followed by PARAFORMALDEHYDE (28.6 g, 954 mmole) and TEA (76 mL, 545 mmole) producing a 15 C exotherm. The solution was heated to 72 C for 2 h. The reaction was cooled to room temperature and poured into Saturated aqueous Ammonium Chloride (500 mL), extracted with ethyl acetate (2 X 150 mL). The combined organic phases were washed with aqueous NAHC03 solution (2 X 150 mL), aqueous 1N HCL solution (2 X 150 mL), and brine (2 X 150 mL), dried OVER NA2S04, filtered and concentrated in vacuo. The crude material was subjected to flash chromatography (Silica, 5% Ethyl ACETATE/HEXANE). Desired fractions were collected and combined, removed solvent in vacuo producing the ethyl ester (27 g, 79%) as a yellow solid. This salicylaldehyde was of suitable purity to use without FURTHER PURIFICATION. HNMR (DMSO-D6/400 MHz) 10.95 (s, 1H), 10.19 (s, 1H), 7.33 (m, 3H), 4.31 (m, 1H).
79%	With triethylamine; magnesium chloride; In acetonitrile; at 10 - 72℃; for 2h;	EXAMPLE 14; (2R)-6-chIoro-5-(3,3-dimethylbutyl)-2-(trifluoromethyl)-l,7b- dihydrocyclopropa[c]chromene-la(2H)-carboxylic acid; Step 1. Preparation of 2-hydroxy-4-iodobenzaldehyde.; [0185] To a chilled solution of commercially available 2-iodophenol (30 g, 136 mmole) in ACN was added MgCl2 (19.5 g, 204 mmole) portion-wise while maintaining the temperature below 10 0C, followed by paraformaldehyde (28.6 g, 954 mmole) and TEA (76 niL, 545 mmole) producing a 15 C exotherm. The solution was heated to 72 0C for 2 h. The reaction was cooled to room temperature and poured into Saturated aqueous Ammonium Chloride (500 mL), extracted with ethyl acetate (2 X 150 niL). The combined organic phases were washed with aqueous NaHCO3 solution (2 X 150 mL), aqueous IN HCl solution (2 X 150 mL), and brine (2 X 150 mL), dried over Na2SO4, filtered and concentrated in vacuo. The crude material was subjected to flash chromatography (Silica, 5% Ethyl acetate/ Hexane). Desired fractions were collected and combined, removed solvent in vacuo producing the ethyl ester (27 g, 79%) as a yellow solid. This salicylaldehyde was of suitable purity to use without further purification. 1HNMR (DMSO-J6/400 MHz) 10.95 (s, IH), 10.19 (s, IH), 7.33 (m, 3H), 4.31 (m, IH).

Reference： [1]Patent: WO2006/40676,2006,A1 .Location in patent: Page/Page column 51
[2]Patent: WO2004/87686,2004,A2 .Location in patent: Page 12-130
[3]Patent: WO2006/40672,2006,A1 .Location in patent: Page/Page column 59

10
[ 38170-02-4 ]
[ 4252-78-2 ]
[ 843646-60-6 ]

Yield	Reaction Conditions	Operation in experiment
23%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 90℃; for 48h;	To a solution of 4-iodo-2-hydroxy-benzaldehyde (5. 4 g, 22 MMOL) and 2-chloro-1- (2, 4-DICHLOROPHENYL) ETHANONE (11.2 g, 50.0 MMOL) in anhydrous N, N-DIMETHYLFORMAMIDE (100 mL) was added K2CO3 (12.0 g, 86.9 MMOL). The dark brown reaction mixture was stirred at 90 C for 48 h, then poured onto water (150 mL) and extracted with ethyl acetate. The solvent was removed under reduced pressure and the residue was purified by column chromatography, eluting with 50% hexanes in dichloromethane. The desired product was obtained as an orange solid (2.06 g, 23%). 1H-NMR (CDCI3) a 7.98 (s, 1 H), 7.70 (dd, J = 8.3, 1.3 Hz, 1 H), 7.54-7. 21 (m, 5H).

Reference： [1]Patent: WO2005/14566,2005,A1 .Location in patent: Page/Page column 77

11
[ 50-00-0 ]
[ 626-02-8 ]
[ 38170-02-4 ]

Yield	Reaction Conditions	Operation in experiment
50%	With triethylamine; magnesium chloride; In acetonitrile;Cooling with ice;	10 g (45 mmol) of 3-iodobenzoic acid was dissolved in 160 ml of anhydrous acetonitrile, 12.8 g (134 mmol) of anhydrous magnesium chloride was added thereto in portions under ice-cooling, followed by addition of 25.3 ml of triethylamine, (636 mmol) of paraformaldehyde was added in batches, and the reaction was quenched by adding 1 M HC1 to adjust the pH to 5. After the reaction, the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and the solvent was passed through 100- 200 mesh silica gel column chromatography, eluting with petroleum ether to give 15.6 g of intermediate, 50% yield
40%	With triethylamine; magnesium chloride; In acetonitrile; at 85℃; for 24h;	In a 100ml reaction bottle,1.5 g (6.8 mmol) of 3-iodophenol and 2 g (21.1 mmol) of anhydrous magnesium chloride were dissolved in 50 ml of anhydrous acetonitrile and 6 ml (43.2 mmol) of triethylamine solution.Then 2g (66.7mmol) of paraformaldehyde was added,The reaction was carried out at 85 C for 24 hours; the reaction was cooled to room temperature.It was then neutralized with 1 N HCl solution and extracted three times with dichloromethane.Drying anhydrous Na2SO4, steaming to obtain crude product,Finally, it was separated and purified by silica gel column chromatography to obtain 0.69 g of product.The yield was 40%.
36%	With triethylamine; magnesium chloride; In acetonitrile;Reflux; Inert atmosphere;	To a dry CH3CN solution (10 mL) of the 1.1 g phenol (5 mmol), anhydrous magnesium chloride (1.42 g, 15 mmol), triethylamine (5.5 mL, 40 mmol) and paraformaldehyde (2.1 g, 70 mmol) were added. The reaction mixture was heated to reflux under an argon atmosphere for overnight and monitored by TLC. Upon cooling, the reaction mixture was dilute with diethyl ether (20 mL). The organic layer was washed successively with HCl (1 M, 210 mL) and water (210 mL), and then dried (MgSO4). The product was puried by column chromatography (PE EA = 50:1) to afford 0.451 g (36%) 4b? as white solid.

		To a solution of 3-iodophenol (3.00 g, 13.6 MMOL) in acetonitrile (50 mL) was added magnesium chloride (3.89 g, 40.9 MMOL), triethylamine (7.6 mL, 55 MMOL), and PARAFORMALDEHYDE (1.64 g, 55 MMOL). The reaction mixture was REFLUXED overnight, then neutralized with saturated aqueous ammonium chloride. The resultant red precipitate was removed by filtration, and the filtrate was extracted with ethyl acetate. The precipitate was dissolved in methanol and added to the combined organic extracts, which were then dried over magnesium sulfate. The solvent was removed under reduced pressure to provide an orange solid (5.4 g) as the crude product. This material was used in the subsequent step without further purification.
		3-Iodophenol (1Og, 45mmol) was dissolved in anhydrous acetonitrile (160ml), cooled in an ice bath and magnesium chloride (12.8g, 134mmol) added portionwise over 1010 mins. Triethylamine (25.3ml, 363mmol) was added to this mixture over 5 mins, followed by portionwise addition of paraformaldehyde (5.47g, 636mmol). After complete addition the mixture was heated at reflux for 18.5 hours. The mixture was cooled and quenched by the addition of sat. NH4Cl (350ml) and extracted with EtOAc (3 xl50ml). The combined EtOAc layers were washed with sat. NaHCO3 (2 x 150mml), IN HCl (2 x 150ml), and sat. NaCl (2 x15 100ml), dried over Na2SO4, filtered and evaporated. The residue was purified by MPLC on silica gel eluting with a gradient rising from 100% hexanes to 20% EtOAc in hexanes. Product containing fractions were combined and evaporated and recrystallised from hot hexanes to give of the title compound. 1HNMR (500 MHz, CDCl3) delta: 11.02 (s, IH), 9.87 (s, IH), 7.46 (d, IH), 7.42 (dd, IH), 7.25 (d, IH).20

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7159 - 7163
[2]Journal of Organic Chemistry,2015,vol. 80,p. 4306 - 4312
[3]Patent: CN104119690,2016,B .Location in patent: Paragraph 0022; 0023; 0024
[4]Canadian Journal of Chemistry,2008,vol. 86,p. 50 - 64
[5]Patent: CN109970696,2019,A .Location in patent: Paragraph 0095-0101
[6]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3057 - 3061
[7]Chemistry - A European Journal,2013,vol. 19,p. 5375 - 5386
[8]Patent: WO2005/14566,2005,A1 .Location in patent: Page/Page column 76-77
[9]Patent: WO2008/57336,2008,A2 .Location in patent: Page/Page column 45-46
[10]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5591 - 5593
[11]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3223 - 3228
[12]Chemical Communications,2017,vol. 53,p. 3645 - 3648
[13]New Journal of Chemistry,2017,vol. 41,p. 9796 - 9805
[14]Journal of Fluorescence,2019,vol. 29,p. 121 - 135

12
[ 25597-16-4 ]
[ 38170-02-4 ]
[ 775328-98-8 ]

Yield	Reaction Conditions	Operation in experiment
52%	With potassium carbonate; In N,N-dimethyl-formamide; at 65℃; for 4h;	Step 2; Preparation of ethyl 7-iodo-2-(trifluoromethyl)-2H-chromene-3- carboxylate; [0169] To a solution of the aldehyde from Step 1 (25 g, 114 mmole) (5 g, 27 mmole) in DMF (50 mL) was added, potassium carbonate (3.79 g, 27.5mmole) and ethyl 4,4,4- trifluorocrotonate (5.08 g, 30 mmole). The mixture was heated to 65 C for 4 h. The reaction was-cooled to room temperature, poured into H2O (150 mL), and extracted with ethyl acetate (2 X 150 mL). The combined organic phases were washed with aqueous NaHCO3 solution (2 X 50 mL), aqueous 3 N HCl solution (2 X 50 mL), and brine (2 X 50 mL), dried over Na2SO4, filtered, and concentrated in vacuo producing the ethyl ester (15 g, 52%) as an amber oil. This ester was of suitable purity to use without further purification

Reference： [1]Patent: WO2006/40676,2006,A1 .Location in patent: Page/Page column 52

13
[ 25597-16-4 ]
[ 38170-02-4 ]
[ 775328-98-8 ]

Yield	Reaction Conditions	Operation in experiment
58%	With potassium carbonate; In N,N-dimethyl-formamide; at 65℃; for 4h;	Step 2. Preparation of ethyl 7-iodo-2-ftrifluoromemyl)-2H-chromene-3-carboxylate.; [0186] To a solution of the benzaldehyde from step 1 (5 g, 27 mrnole) in DMF (50 niL) was added, potassium carbonate (3.79 g, 27.5mmole) and ethyl 4,4,4- trifluorocrotonate (5.08 g, 30 mmole). The mixture was heated to 65 C for 4 h. The reaction was cooled to room temperature, poured into H2O (150 mL), and extracted with ethyl acetate (2 X 150 mL). The combined organic phases were washed with aqueous NaHCO3 solution (2 X 50 mL), aqueous 3 N HCl solution (2 X 50 mL), and brine (2 X 50 mL), dried over Na2SO4, filtered, and concentrated in vacuo producing the title compound (58%). This ester was of suitable purity to use without further purification: ESHRMS m/z 361.1040 (M-H, C13H9IF3O3, Calc'd 361.1046).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7159 - 7163
[2]Patent: WO2006/40672,2006,A1 .Location in patent: Page/Page column 60

14
[ 1785-61-1 ]
[ 38170-02-4 ]
[ 1005238-04-9 ]

Reference： [1]Canadian Journal of Chemistry,2008,vol. 86,p. 50 - 64

15
[ 38170-02-4 ]
[ 75867-46-8 ]
[ 1005238-05-0 ]

Reference： [1]Canadian Journal of Chemistry,2008,vol. 86,p. 50 - 64

16
[ 38170-02-4 ]
[ 100-39-0 ]
[ 854028-52-7 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 20 - 50℃; for 4.25h;	To a solution of 2-hydrox -4-iodobenzaldehyde (i-45) (5g, 20.2mmol) in anhydrous acetonitrile (25ml) was added l,8-diazabicyclo[5.4.0]undec-7-ene (3.2ml, 21.2mmol), 25 followed by benzyl bromide (2.53ml, 21.2mmol). The mixture was stirred at room temperature for 15 mins then warmed at 5O0C for 4 hours. The cooled reaction mixture was evaporated. The residue was partitioned between IN HCl (150ml) and Et2O (150ml), and extracted with Et2O (3 x 150ml). The combined Et2O layers were washed with water (150ml), sat. NaCl (150ml), dried over MgSO4, filtered and evaporated. The residue was recrystallized from EtOAc/hexanes to EPO <DP n="47"/>give of the title compound. 1PiNMR (500 MHz, CDCl3) delta: 10.50 (s, IH), 7.58 (d, IH), 7.50-7.38 (m, 7H), 5.19 (s, 2H).

Reference： [1]Patent: WO2008/57336,2008,A2 .Location in patent: Page/Page column 45-46

17
[ 38170-02-4 ]
[ 1779-49-3 ]
[ 924708-48-5 ]

Yield	Reaction Conditions	Operation in experiment
98%		Example 8; Preparation of Haloorganic Compound for Use in Total Synthesis of Ratanhine; Haloorganic compound 15 was synthesized by a multi-step process. To a mixture of methyltriphenylphosphonium bromide (14.08 g, 39.4 mmol) in toluene at 23 C. was added a solution of potassium tert-butoxide (4.47 g, 39.8 mmol) in THF (60 mL) dropwise via cannula, and the resulting mixture was allowed to stir at 23 C. for 4 hours. The resulting yellow mixture was cooled to -78 C. and a solution of 4-iodo-salicylaldehyde (4.35 g, 17.5 mmol) in toluene (40 mL) was added dropwise via cannula. The resulting mixture was allowed to slowly warm to 23 C. and was stirred at that temperature for 12 hours. The reaction was then quenched with the addition of saturated aq. ammonium chloride (100 mL). The resulting mixture was then diluted with water (200 mL) and extracted with Et2O (3×100 mL). The combined organic fractions were then washed with brine (100 mL), dried over magnesium sulfate, and concentrated in vacuo. Purification by flash chromatography (SiO2, hexanes:ethyl acetate 7:1?1:1) yielded 2-hydroxy-5-iodostyrene as a colorless solid (4.0 g, 98%). See also Gligorich, K. M., 2006.

Reference： [1]Patent: US2009/30238,2009,A1 .Location in patent: Page/Page column 15-16

18
[ 38170-02-4 ]
[ 105-36-2 ]
[ 1089681-88-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5591 - 5593

19
[ 38170-02-4 ]
[ 54663-78-4 ]
[ 1118519-87-1 ]

Reference： [1]Canadian Journal of Chemistry,2009,vol. 87,p. 314 - 320

20
[ 50-00-0 ]
[ 626-02-8 ]
[ 38169-97-0 ]
[ 38170-02-4 ]

Yield	Reaction Conditions	Operation in experiment
		The reaction was carried out in a large flask equipped with a stirrer and reflux condenser. A solution of 3-Iodophenol (1Og; 45,4 mmol) in acetonitrile (160 ml) was cooled in an ice-water bath and magnesium chloride (12.8g; 134.4 mmol) was added to the phenol in small batches over 10 minutes to give a pink cloudy solution. Triethylamine (50.6 ml; 363.2 mmol) was added to the acetonitrile solution gradually over 5 minutes keeping the solution at ~0 0C and this was followed with the addition of paraformaldehyde (19.2g; 636 mmol) in small 0.5-lg batches over 10 minutes. Once the addition of the paraformaldehyde was complete the reaction vessel with the reflux condenser in place was removed from the cooling bath and warmed quickly to 80 0C (bath temperature). After 0.25 h of heating the solids started to dissolve and around 1 h of heating the reaction solution was almost a homogeneous golden yellow color which slowly started to turn to an orange color. The reaction was kept at 80 0C for 18.5 hours; the reaction had become a deep orange in color. The reaction mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride solution (350 ml). The aqueous acetonitrile mixture was shaken with EtOAc (150 ml) and transferred into a separatory funnel. The layers were separated and the aqueous layer extracted with EtOAc (2 x 150 ml). The three EtOAc layers were combined and washed successively with saturated aqueous NaHCO3 (2 x 150 ml), IN hydrochloric acid (2 x 150 ml) and lastly with saturated brine (2 x 100 ml). The orange colored solution with the crude product was dried over anhydrous Na2SO4 powder, filtered through a Celite pad and the filtrate concentrated under reduced pressure to leave an orange colored oil that slowly solidified on standing. The solid was purified in 3 batches on a Biotage SPl system on 4OM Flash silica cartridge using a gradient of EtOAc and hexanes 0->2% (350 ml), 2->15% (1250 ml) 15->20% (350 ml). The aldehyde fractions were concentrated down to leave an off-white feathery solid. This solid was crystallized from hexanes to give 6g of the pure aldehyde. The mother liqours were purified on silica gel preparative tic plates eluted with EtOAc and hexanes (7:93 v/v) from which a further 300 of the desired aldehyde was recovered (Total 6.3g). There was also -800 mg of the isomeric aldehyde obtained from the purification. The NMR data for 2-hydroxy-4-iodobenzaldehyde is as follows :- 1H-NMR (400 MHz, CDCl3) delta: 7.25 (d, J = 8 Hz, IHO, 7.42 (dd, J = 8 & 1.5 Hz, IH), 7.46 (d, J - 1.5Hz, IH), 9.87 (s, IH)5 11.04 (s, IH).The NMR data for the isomeric 2-hydroxy-6-iodobenzaldehyde was:- 1H-NMR (400 MHz, CDCl3) delta: 6.99 (d, J = 8 Hz, IH), 7.15 (t, J = 8 Hz, IH)3 7.50 (d, J = 8 Hz, IH), 10.09 (s, IH), 12.07 (s, IH).

Reference： [1]Patent: WO2010/56788,2010,A1 .Location in patent: Page/Page column 89-90

21
[ 556-56-9 ]
[ 38170-02-4 ]
[ 1227268-30-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 20 - 65℃;	AUyI iodide (2.32 ml; 25.4 mmol) was added over 5 minutes drop by drop to a solution of <strong>[38170-02-4]2-hydroxy-4-iodobenzaldehyde</strong> (6g; 24.2 mmol) from Example 16 Step A above and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (3.83 ml; 25.4 mmol) in dry acetonitrile (30 ml). The resulting reaction mixture was heated to 65 0C and maintained at that temperature for 3.5 hours. The volatiles were then removed under reduced pressure on a rotary evaporator to leave a golden yellow oil. The oil was carefully partitioned between 2N-hydrochloric acid (100 ml) and diethyl ether (3 x 100 ml). The ethereal extracts were combined and then dried over anhydrous MgSO4 powder, filtered and the ethereal filtrates concentrated under reduced pressure to obtain an off white solid. The solid was triturated with a small volume of hexanes and ether (9:1 v/v). The solid material was filtered off at the pump on a filter paper in a Buchner funnel, washed with a small amount of hexanes and ether (9: 1 v/v) and dried to constant weight. 2 -(Allyloxy)-4- iodobenzaldehyde was isolated as an off white solid that had the following NMR spectrum. 1H- NMR (400 MHz, CDCl3) delta: 4.66 (dt, J - 5 & 1.5 Hz, 2H), 5.38 (dq, J = 1 1.5 & 1.5 Hz, IH), 5.47 (dq, J = 17.5, 1.5 Hz, IH), 6.08 (ddt, J = 17.5 & 11.5 & 5 Hz, IH), 7.37(d; J =1 Hz, IH), 7.43 (d, J = 8 Hz, IH), 7.54 ( d, J = 8 Hz5 IH), 10.46 (s, IH).

Reference： [1]Patent: WO2010/56788,2010,A1 .Location in patent: Page/Page column 90

22
[ 38170-02-4 ]
[ 1300036-84-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1849 - 1851

23
[ 38170-02-4 ]
C₃₂H₂₇IN₂O₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1849 - 1851

24
[ 38170-02-4 ]
[ 1300036-85-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1849 - 1851

25
[ 38170-02-4 ]
Na⁽¹⁺⁾*SO₃C₄(CH₃)2NCHC₃ON₂CH₃BF₂C₆H₄C₂C₆H₃OCH₂COOHCBF₂(C₄H₂NC₆H₄OCH₃)2^(1-)=NaSO₉N₅F₄B₂H₃₈C₅₀ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1849 - 1851

26
[ 38170-02-4 ]
[ 1300036-86-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1849 - 1851

27
[ 38170-02-4 ]
[ 96-32-2 ]
[ 1300026-62-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1849 - 1851

28
[ 38170-02-4 ]
[ 21962-45-8 ]