1583-59-1|2,2-Difluorobenzo[d][1,3]dioxole| Ambeed

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Structure of 1583-59-1

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Quality Control of [ 1583-59-1 ] Purity: 98% SDS Specification

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Product Details of [ 1583-59-1 ]

CAS No. :	1583-59-1
Formula :	C₇H₄F₂O₂
M.W :	158.10
SMILES Code :	FC1(F)OC2=CC=CC=C2O1
MDL No. :	MFCD00236217
InChI Key :	DGCOGZQDAXUUBY-UHFFFAOYSA-N
Pubchem ID :	74103

Safety of [ 1583-59-1 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H225-H315-H317
Precautionary Statements:	P210-P233-P240-P241-P242-P243-P261-P264-P272-P280-P303+P361+P353-P333+P313-P370+P378-P403+P235-P501
Class:	3
UN#:	1993
Packing Group:	Ⅱ

Computational Chemistry of [ 1583-59-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.14
Num. rotatable bonds	0
Num. H-bond acceptors	4.0
Num. H-bond donors	0.0
Molar Refractivity	32.65
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	18.46 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.97
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.5
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.85
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.49
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.32
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.23

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.8
Solubility	0.251 mg/ml ; 0.00159 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.53
Solubility	0.463 mg/ml ; 0.00293 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.68
Solubility	0.327 mg/ml ; 0.00207 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.49 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.24

Application In Synthesis of [ 1583-59-1 ]

* 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.

Downstream synthetic route of [ 1583-59-1 ]

[ 1583-59-1 ] Synthesis Path-Downstream 1~36

2
[ 75-21-8 ]
[ 1583-59-1 ]
[ 334778-39-1 ]

Yield	Reaction Conditions	Operation in experiment
38%		2,2-Difluoro-1,3-benzodioxole (0.56 mL, 5.0 mmol) was added to a solution of sec-butyllithium (in THF, 10 mL, 5.0 mmol) in cyclohexane at -78 C. The reaction mixture was treated with ethylene oxide (2.2 g, 50 mmol) and allowed to warm to 23 C. After 2 h, the reaction mixture was diluted with ether (100 mL), washed with water (5×25 mL) then brine (2×25 mL). The organic layer was dried (Na2SO4), concentrated in vacuo and the residue was purified by silica gel column chromatography (5-50% EtOAc in hexanes) to yield 2-(2,2-difluorobenzo[1,3]dioxol-4-yl)ethanol (286 mg, 38%).

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.
[2]European Journal of Organic Chemistry,2001,p. 691 - 695.
[3]Patent: US2006/211603,2006,A1 .Location in patent: Page/Page column 64-65.

3
[ 1583-59-1 ]
[ 124-38-9 ]
[ 126120-85-2 ]

References: [1]European Journal of Organic Chemistry,2001,p. 691 - 695.

4
[ 503-30-0 ]
[ 1583-59-1 ]
[ 531508-38-0 ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

5
[ 50-00-0 ]
[ 1583-59-1 ]
[ 157437-25-7 ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

6
[ 1583-59-1 ]
[ 127333-93-1 ]
4-(2,2-difluoro-1,3-dioxol-4-yl)-1-butanol [ No CAS ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

7
[ 1583-59-1 ]
fluorodimethoxyborane-diethyl etherate [ No CAS ]
dimethoxy-(2,2-difluoro-1,3-benzodioxol-4-yl)borane [ No CAS ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

8
[ 1583-59-1 ]
[ 144584-66-7 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; bromine; In tetrahydrofuran; hexane; water;	STR15 To 15.8 g (0.1 mol) of <strong>[1583-59-1]2,2-difluorobenzodioxole</strong> (compare e.g. DE-OS (German Published Specification) 19 21 741) in 80 ml of absolute tetrahydrofuran are added dropwise under a dry nitrogen atmosphere at -78 C. within 1 hour with stirring 45 ml (0.11 mol) of n-butyllithium (2.5 molar in n-hexane), and after stirring for 1 hour at -78 C. 16 g (0.1 mol) of bromine are then added dropwise with stirring at -78 C. The mixture is stirred for a further 90 minutes at -78 C. then allowed to come to room temperature, and is hydrolyzed with 75 ml of 10 per cent hydrochloric acid. For work-up the organic phase is separated off, washed with 1 normal hydrochloric acid, dried over sodium sulphate, concentrated in vacuo and the residue is distilled in a water pump vacuum. 11.3 g (46% of theory) of 4-bromo-<strong>[1583-59-1]2,2-difluorobenzodioxole</strong> are obtained of boiling point 74 C. to 75 C. at 20 mbar.

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.
[2]Patent: US5258526,1993,A .

9
[ 1583-59-1 ]
4-azido-2,2-difluoro-1,3-benzodioxole [ No CAS ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

10
[ 1583-59-1 ]
[ 106876-54-4 ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.
[2]European Journal of Organic Chemistry,2003,p. 452 - 462.
[3]Patent: CN109020964,2018,A .
[4]Patent: CN109020965,2018,A .
[5]Patent: CN109053703,2018,A .

11
[ 1583-59-1 ]
[ 531508-54-0 ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

12
[ 1583-59-1 ]
[ 68-12-2 ]
[ 119895-68-0 ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

13
[ 1583-59-1 ]
[ 79-22-1 ]
[ 531508-32-4 ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

14
[ 1583-59-1 ]
[ 95-92-1 ]
ethyl (2,2-difluoro-1,3-benzodioxol-4-yl)oxoacetate [ No CAS ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

15
[ 1583-59-1 ]
[ 77-78-1 ]
[ 72769-03-0 ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

16
[ 75-77-4 ]
[ 1583-59-1 ]
[ 126120-90-9 ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

17
[ 75-77-4 ]
[ 1583-59-1 ]
[ 663934-11-0 ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

18
[ 1583-59-1 ]
[ 994-30-9 ]
[ 663934-00-7 ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

19
[ 2032-75-9 ]
[ 1583-59-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen fluoride; at 0 - 50℃; under 4 - 5 Torr;	1040g of mixture obtained with the reaction of step (a) were introduced into a 3-litre steel reactor, and the system was cooled to 0-3C under stirring. Metering of the hydrofluoric acid in portions of 70 ml each for a total amount of 280 g was started. During addition, the vent of the reactor was left open; at the end of the addition it was re-closed, and the internal pressure was allowed to rise to 4-5 atm. After approximately 15 minutes following upon each addition, the hydrochloric acid formed was vented, and a fresh addition of hydrofluoric acid was made. At the end of this addition, the reaction mixture was heated to approximately 50C to remove any excess of hydrofluoric acid. The product was purified by distillation, first eliminating the residual hydrofluoric acid, and rectification was performed to obtain the product of the titre. There were obtained 1805 g of the product with a purity of 99.9 % (GC). The global yield of chlorination, fluorination and distillation was 83%.
	With 2,4-dichloro-benzotrifluoride; hydrogen fluoride; at 0 - 50℃; under 3040.2 - 3800.26 Torr;	846 g of mixture obtained with the reaction of step (a) were introduced in a 3-litre steel reactor, and the system was cooled to 0-4C under stirring. Metering of the hydrofluoric acid in portions (70 ml, 80 ml, 80 ml) was started for a total amount of 230 g. During the addition, the vent of the reactor was left open; at the end of the addition, it was re-closed, and the internal pressure was allowed to rise to 4-5 atm. After approximately 15 minutes following upon each addition, the hydrochloric acid formed was vented, and a new addition of hydrofluoric acid was performed. At the end of this operation, the reaction mixture was heated to approximately 50C to remove the excess hydrofluoric acid. The product was purified by distillation, first eliminating the residual hydrofluoric acid, and rectification was then performed to obtain the product of the titre. There were obtained 373 g, with a purity of 99.9 % (GC). The global yield of chlorination, fluorination and distillation was 85%.
28.8 g	With hydrogen fluoride; for 2h;	24 ml (0.2 mol) of a pepper ring was added to a 250 ml lined PTFE stainless steel flask,Phosphonium chloride 97.6g and phosphorus pentachloride 83.3g (0.4m0l), the temperature rose to reflux reaction, GC detection of raw material pepper ring content of less than 0.2% reaction end; the reaction solution distillation distillation distillation of by-product three Phosphorus chloride and solvent phosphorus oxychloride, vacuum distillation temperature of 110 C, vacuum degree of -0.095MPa; vacuum distillation after the end of cooling to 4 C, in the vacuum of -0.095MPa drop Plus hydrogen fluoride liquid 8g (0.4mol), dropping finished, incubated for 2 hours, and then release the by-product of hydrogen chloride, and then add saturated sodium carbonate solution, adjust the solution PH value of 6.5 ~ 7.5, stirring 0.5 hours, , The organic layer was distilled after the colorless transparent liquid for the finished 2,2 - difluoro - 1, 3 - benzodiazepine 28.8g, yield 99.8%, GC purity 99.8%

References: [1]Journal of Fluorine Chemistry,2006,vol. 127,p. 85 - 90.
[2]Patent: EP1502908,2005,A1 .Location in patent: Page 4.
[3]Patent: EP1502908,2005,A1 .Location in patent: Page 4.
[4]Patent: CN106810530,2017,A .Location in patent: Paragraph 0008; 0011.

20
[ 1583-59-1 ]
[ 33070-32-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	With bromine; In water; at 25 - 85℃; for 9h;Reflux;	2, 2-difluoro-l, 3-benzodioxole (200g, 1.27mol) and water (456g, 25.3mol) were placed in a 1000 mL round -bottomed flask fitted with a mechanical stirrer, reflux condenser and pressure equalizing addition funnel. Bromine (284g, 1.77mol) was added drop-wise at 25C for one hour. During addition, the temperature of the mass was raised from 25C to 85C. The temperature of the reaction mass was maintained at 85C for 8 hours. The progress of the reaction was monitored by liquid chromatography. The temperature of the reaction mass was brought down to 25C. The layers were separated, the organic layer was washed with sodium bisulphite solution followed by sodium bicarbonate solutionto obtain the title compound. The crude mass was purified by vacuum distillation. Yield (%) : 80 Purity (%) : 99.8 (by liquid chromatography)
75%	With bromine; iron; at 20 - 30℃;Inert atmosphere; Large scale;	250.0 kg (1.581 kmol) of <strong>[1583-59-1]2,2-difluorobenzodioxole</strong> was placed in a 500 L lined PTFE enamel kettle, and 25.0 kg of iron filings were added under stirring, and the inside of the kettle was replaced with nitrogen. The reaction temperature was controlled at 20 to 30 C, and 250.0 kg (1.564 kmol) of bromine was added dropwise over 8 to 10 hours, and the tail gas was absorbed by liquid alkali. After the completion of the reaction, the reaction system was pumped into another 2000 L reaction vessel containing 1000 kg of cold water, and the temperature was controlled to 30 C or lower. The reaction was quenched by dropwise addition of 100 kg of 25% sodium hydrogen sulfite solution, and the pH of the system was adjusted to 8-9 by dropwise addition of 32% liquid alkali. The temperature was raised to 100 C and the product was distilled off by steam distillation. Approximately 310 kg of a crude 5-bromo-2,2-difluoropipepene ring was obtained, and further separated to obtain a 5-bromo-<strong>[1583-59-1]2,2-difluorobenzodioxole</strong> 250 kg (1.181 kmol), a purity of 99%, and a yield of 75%.
538 g	With hydrogen bromide; dihydrogen peroxide; at 10 - 70℃;	Example 1Process of preparation of 5-bromo-<strong>[1583-59-1]2,2-difluoro-1,3-benzodioxole</strong> A mixture of 2,2-difluoro-l ,3-benzodioxote (560 g) and Hydrogen bromide(l 100 g, Assay 47%) were taken in a reaction vessel fitted with cold condenser. The reaction mixture was cooled to 10C and 30 % Hydrogen Peroxide solution (806 g) was added slowly in lot wise. Upon completion of addition, the temperature of the reaction mixture was cautiously raised to 70C. The organic layer was separated and washed with 20 % of sodium metabisulfite and then washed with 20% of potassium bicarbonate solution. The organic layer was dried over magnesium sulfate and filtered. The filtrate was distilled under high vacuum to obtain the title compound. Yield: 538 g

References: [1]Patent: WO2017/46816,2017,A2 .Location in patent: Page/Page column 9-10.
[2]Patent: CN109503544,2019,A .Location in patent: Paragraph 0042-0044.
[3]Patent: EP1595877,2005,A1 .Location in patent: Page/Page column 4.
[4]European Journal of Organic Chemistry,2004,p. 64 - 68.
[5]Patent: WO2016/38627,2016,A1 .Location in patent: Page/Page column 4.

21
[ 1583-59-1 ]
5-bromo-2,2-difluoro-1,3-benzodioxole-4-carboxylic acid [ No CAS ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

22
[ 1583-59-1 ]
[ 663934-09-6 ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

23
[ 1583-59-1 ]
2,2-difluoro-5-iodobenzo[d][1,3]dioxole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With N-iodo-succinimide; methanesulfonic acid; In dichloromethane; at 20℃; for 12h;	To a solution of <strong>[1583-59-1]2,2-difluoro-1,3-benzodioxole</strong> (1.50 mL, 12.4 mmol) and methanesulfonic acid (4.02 mL, 62.0 mmol) in dichloromethane (12.4 mL)N-iodosuccinimide (2.79 g, 12.4 mmol) was added at room temperature,And the mixture was stirred for 12 hours.A 15% sodium hydroxide aqueous solution was added to the reaction solution at 0 C. to adjust the pH of the reaction solution to 9, followed by extraction with chloroform.The organic layer was washed with an aqueous sodium thiosulfate solution,After drying over anhydrous sodium sulfate, it was concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane)2,2-Difluoro-5-iodo-1,3-benzodioxoleOf a colorless oily substance (3.23 g, yield: 91%).

References: [1]Patent: JP2015/848,2015,A .Location in patent: Paragraph 0257-0259.
[2]European Journal of Organic Chemistry,2004,p. 64 - 68.

24
[ 1583-59-1 ]
[ 663934-15-4 ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

25
[ 1583-59-1 ]
[ 663934-13-2 ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

26
[ 1583-59-1 ]
(6-bromo-2,2-difluoro-1,3-benzodioxol-4-yl)trimethylsilane [ No CAS ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

27
[ 1583-59-1 ]
2,2-difluoro-7-iodo-1,3-benzodioxole-4-carboxylic acid [ No CAS ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

28
[ 1583-59-1 ]
2,2-difluoro-6-iodo-1,3-benzodioxole-4-carboxylic acid [ No CAS ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

29
[ 1583-59-1 ]
[ 663934-02-9 ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

30
[ 1583-59-1 ]
2,2-difluoro-5,7-diiodo-1,3-benzodioxole-4-carboxylic acid [ No CAS ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

31
[ 1583-59-1 ]
[ 663934-04-1 ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

32
[ 1583-59-1 ]
5-bromo-2,2-difluoro-7-trimethylsilyl-1,3-benzodioxole-4-carboxylic acid [ No CAS ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

33
[ 1583-59-1 ]
[ 663934-07-4 ]

References: [1]European Journal of Organic Chemistry,2004,p. 64 - 68.

34
[ 1583-59-1 ]
2,2-difluoro-7-methyl-1,3-benzodioxole-4-carboxylic acid [ No CAS ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

35
[ 1583-59-1 ]
[ 334778-39-1 ]

References: [1]European Journal of Organic Chemistry,2003,p. 452 - 462.

36
[ 1583-59-1 ]
2,2-difluoro-2H-1,3-benzodioxol-4-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%		Example 39A 2,2-difluoro-2H-1,3-benzodioxol-4-ol A solution of <strong>[1583-59-1]2,2-difluoro-1,3-benzodioxole</strong> (0.230 mL, 2.53 mmol) in tetrahydrofuran (4 mL) was cooled to <-70 C. and sec-butyllithium (1.988 mL, 2.78 mmol) was added dropwise at <-68 C. After 2 hours, trimethyl borate (0.339 mL, 3.04 mmol) was added at <-65 C. (exothermic, dropwise addition), and the mixture was then warmed to ambient temperature. Hydrogen peroxide (0.503 mL, 5.06 mmol) and sodium hydroxide (101 mg, 2.53 mmol) were added and after 20 minutes, the reaction temperature was raised to 50 C. for an additional 25 minutes. Water (2 mL) was added to give a homogeneous biphasic mixture. The mixture was extracted with tert-butyl methyl ether (320 mL) and ethyl acetate (220 mL). The combined organic fractions were extracted with 2 N NaOH (3*10 mL). The combined aqueous fractions were acidified with 2 N HCl (40 mL) and extracted with tert-butyl methyl ether (150 mL). This organic phase was combined with the previous organic fractions, and the combined fractions were dried (Na2SO4) and concentrated. The residue was purified by flash chromatography on silica gel, eluted with 0-50% tert-butyl methyl ether/heptanes to obtain the title compound (364 mg, 2.091 mmol, 83% yield). 1H NMR (400 MHz, CDCl3) delta ppm 6.93 (t, J=8.3 Hz, 1H), 6.67 (m, 2H), 5.84 (br s, 1H).
		Intermediate 1982,2-difluoro-l,3-benzodioxol-4-ol2,2-Difluoro-l,3-benzodioxole (320 mg, 2.05 mmol) was dissolved in THF (2.5 mL) and cyclohexane (1.2 mL) and the resulting solution cooled down to -78C. sec-BuLi 2M solution in cyclohexane (1.025 ml,2.05 mmol) was added drop wise and the reaction mixture stirred for 2 hours at -78 C. Trimethylborate (230mg, 2.25 mmol) was added and the mixture was allowed to warm slowly to room temperature A 30 % w/w aqueous solution of H202 (4.1 mmol) and NaOH (82 mg, 2.05 mmol) were added and the reaction mixture stirred for 18 hours at room temperature. The reaction was quenched with a 2N aqueous solution of HCI and diluted with ethyl acetate. Two phases were separated and the organic layer was washed twice with brine, dried over Na2S04 and evaporated to dryness, affording the title compound (340 mg).XH-NMR (400 MHz, CDCI3): delta ppm 6.93 (1H, t), 6.69 (1H, d), 6.65 (1H, d). 19F-NMR (376 MHz, CDCI3): delta ppm -49.86. 13C-NMR (200 MHz, CDCI3): delta ppm 144.8, 139.6, 131.5 (t, =255.1 Hz), 131.2, 123.9, 112.7, 101.8
340 mg		Intermediate 198 2,2-difluoro-1,3-benzodioxol-4-ol [1083] [1084] 2,2-Difluoro-1,3-benzodioxole (320 mg, 2.05 mmol) was dissolved in THF (2.5 mL) and cyclohexane (1.2 mL) and the resulting solution cooled down to -78 C. sec-BuLi 2M solution in cyclohexane (1.025 ml, 2.05 mmol) was added drop wise and the reaction mixture stirred for 2 hours at -78 C. Trimethylborate (230 mg, 2.25 mmol) was added and the mixture was allowed to warm slowly to room temperature. A 30% w/w aqueous solution of H2O2 (4.1 mmol) and NaOH (82 mg, 2.05 mmol) were added and the reaction mixture stirred for 18 hours at room temperature. The reaction was quenched with a 2N aqueous solution of HCl and diluted with ethyl acetate. Two phases were separated and the organic layer was washed twice with brine, dried over Na2SO4 and evaporated to dryness, affording the title compound (340 mg). [1085] 1H-NMR (400 MHz, CDCl3): delta ppm 6.93 (1H, t), 6.69 (1H, d), 6.65 (1H, d). 19F-NMR (376 MHz, CDCl3): 6 ppm -49.86. 13C-NMR (200 MHz, CDCl3): delta ppm 144.8, 139.6, 131.5 (t, J=255.1 Hz), 131.2, 123.9, 112.7, 101.8

References: [1]Patent: US2017/15675,2017,A1 .Location in patent: Paragraph 1051.
[2]European Journal of Organic Chemistry,2003,p. 452 - 462.
[3]Patent: WO2012/76877,2012,A1 .Location in patent: Page/Page column 169.
[4]Patent: US2013/267510,2013,A1 .Location in patent: Paragraph 1083-1085.

Historical Records

Technical Information

• Alkyl Halide Occurrence • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Friedel-Crafts Reaction • Hydrogenolysis of Benzyl Ether • Preparation of Alkylbenzene • Reactions of Benzene and Substituted Benzenes • Vilsmeier-Haack Reaction

Related Functional Groups of
[ 1583-59-1 ]

Fluorinated Building Blocks

A130973 [53104-96-4]

2-(Difluoromethoxy)phenol

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A128809 [33070-32-5]

5-Bromo-2,2-difluorobenzodioxole

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A111982 [32858-93-8]

2-(Trifluorormethoxy)phenol

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A377087 [656-42-8]

2,2-Difluorobenzo[d][1,3]dioxole-5-carbaldehyde

Similarity: 0.76

A513974 [458-92-4]

(Difluoromethoxy)benzene

Similarity: 0.76

Related Parent Nucleus of
[ 1583-59-1 ]

Other Aromatic Heterocycles

A128809 [33070-32-5]

5-Bromo-2,2-difluorobenzodioxole

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A377087 [656-42-8]

2,2-Difluorobenzo[d][1,3]dioxole-5-carbaldehyde

Similarity: 0.76

A172145 [68119-31-3]

2-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)acetonitrile

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A180115 [531508-54-0]

2,2-Difluoro-4-iodobenzo[d][1,3]dioxole

Similarity: 0.75

A210984 [274-09-9]

Benzo[d][1,3]dioxole

Similarity: 0.74

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CAS No.: 1583-59-1

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