5-Fluoro-2-methoxybenzaldehyde | Benzene Compounds

Structure of 5-Fluoro-2-methoxybenzaldehyde
CAS No.: 19415-51-1

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Synonyms: 5-Fluoro-O-Anisaldehyde

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Quality Control of [ 19415-51-1 ] Purity: 98% SDS Specification

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Product Details of [ 19415-51-1 ]

CAS No. :	19415-51-1
Formula :	C₈H₇FO₂
M.W :	154.14
SMILES Code :	C1=C(C(=CC(=C1)F)C=O)OC
Synonyms :	5-Fluoro-O-Anisaldehyde
MDL No. :	MFCD00143458
InChI Key :	CRLDWFVRQNUUSZ-UHFFFAOYSA-N
Pubchem ID :	2734943

Safety of [ 19415-51-1 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 19415-51-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.12
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	38.28
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	26.3 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.79
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	2.04
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.07
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.	1.55
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	2.39
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.97

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.35
Solubility	0.685 mg/ml ; 0.00444 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.	-2.22
Solubility	0.928 mg/ml ; 0.00602 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	-2.74
Solubility	0.282 mg/ml ; 0.00183 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.	-5.79 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	1.0 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)	1.23

Application In Synthesis of [ 19415-51-1 ]

* 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 [ 19415-51-1 ]

[ 19415-51-1 ] Synthesis Path-Downstream 1~54

1
[ 2591-86-8 ]
[ 452-08-4 ]
[ 19415-51-1 ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 1385 - 1392.
[2]Journal of Organic Chemistry,2013,vol. 78,p. 5955 - 5963.

2
[ 459-60-9 ]
[ 542-88-1 ]
[ 19415-51-1 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 2001 - 2016.

3
[ 7677-24-9 ]
[ 19415-51-1 ]
[ 82128-83-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	zinc diiodide; In dichloromethane;	EXAMPLE 13 2-(5-Fluoro-2-methoxyphenyl)-2-trimethylsiloxyethanenitrile By the procedure of Example 1, except that a reaction time of 4 days at room temperature was employed, <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> (9.5 g., 0.062 mole) in 50 ml. of methylene chloride was reacted with trimethylsilylcarbonitrile (7.3 g., 0.074 mole) in the presence of a catalytic amount of zinc iodide to produce 2-(5-fluoro-2-methoxyphenyl)-2-trimethylsiloxyethanenitrile [12.5 g., 79%; oil; m/e 253; ir (CH2 Cl2) 1504, 1200 cm-1 ].
79%	With zinc(II) iodide; at 20℃; for 1h;	A solution of ZnI2 (1.6 mg, 0.01 mmol), <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> (1.54 g, 9.99 mmol) in trimethylsilanecarbonitrile (1.5 mL, 11.25 mmol) was stirred for 1 h at room temperature. The resulting mixture was concentrated under vacuum. The resulting crude product was purified by silica gel chromatography (eluting with 1:1 ethyl acetate/petroleum ether) to afford 2-(5-fluoro-2-methoxyphenyl)-2-[(trimethylsilyl)oxy]acetonitrile as a white solid (2.0 g, 79%).

References: [1]Patent: US4367234,1983,A .
[2]Patent: WO2019/55877,2019,A1 .Location in patent: Paragraph 0419.
[3]Journal of Medicinal Chemistry,1986,vol. 29,p. 770 - 778.

4
[ 141-82-2 ]
[ 19415-51-1 ]
[ 157518-45-1 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 461 - 470.

5
[ 19415-51-1 ]
[ 35160-95-3 ]
[ 94569-80-9 ]

References: [1]Journal of Organic Chemistry,1985,vol. 50,p. 457 - 461.

6
[ 19415-51-1 ]
[ 151-50-8 ]
[ 506-87-6 ]
[ 120121-08-6 ]

References: [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 1208 - 1213.

7
[ 19415-51-1 ]
[ 84194-48-9 ]
[ 94569-78-5 ]

References: [1]Journal of Organic Chemistry,1985,vol. 50,p. 457 - 461.

8
[ 19415-51-1 ]
[ 126209-85-6 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 2001 - 2016.

9
[ 19415-51-1 ]
protonated 5-fluoro-2-methoxybenzaldehyde [ No CAS ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 1385 - 1392.

10
[ 19415-40-8 ]
[ 19415-51-1 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 461 - 470.
[2]Chimica Therapeutica,1968,vol. 3,p. 1 - 9.

11
[ 459-60-9 ]
[ 68-12-2 ]
[ 19415-51-1 ]

References: [1]Journal of Organic Chemistry,1988,vol. 53,p. 3145 - 3147.
[2]Journal of Organic Chemistry,1988,vol. 53,p. 3145 - 3147.

12
[ 459-60-9 ]
[ 68-12-2 ]
[ 19415-51-1 ]
[ 105728-90-3 ]

References: [1]Journal of Organic Chemistry,1988,vol. 53,p. 3145 - 3147.

13
[ 19415-51-1 ]
cis-(+/-)-2-phenylpiperidin-3-ylamine [ No CAS ]
(5-Fluoro-2-methoxy-benzyl)-((2R,3R)-2-phenyl-piperidin-3-yl)-amine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4985 - 4992.

14
[ 179556-97-9 ]
[ 19415-51-1 ]
4-[(5-fluoro-2-methoxy-benzyl)-isobutyl-amino]-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2714 - 2718.

15
[ 19415-51-1 ]
[ 4440-01-1 ]
1-(5-fluoro-2-methoxy-phenyl)-3-phenyl-prop-2-yn-1-ol [ No CAS ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 1626 - 1632.

16
[ 858279-61-5 ]
[ 19415-51-1 ]
N'-(7-chloro-quinolin-4-yl)-N-(5-fluoro-2-methoxy-benzyl)-N-propyl-propane-1,3-diamine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4535 - 4543.

17
[ 908243-22-1 ]
[ 19415-51-1 ]
N'-(7-chloro-quinolin-4-yl)-N-(5-fluoro-2-methoxy-benzyl)-N-propyl-butane-1,4-diamine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4535 - 4543.

18
[ 19415-51-1 ]
[ 140-88-5 ]
C₁₃H₁₅FO₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3431 - 3434.

19
[ 19415-51-1 ]
[ 945013-31-0 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3431 - 3434.

20
[ 19415-51-1 ]
C₁₃H₁₆FNO₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3431 - 3434.

21
[ 19415-51-1 ]
C₁₁H₁₂FNO₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3431 - 3434.

22
[ 19415-51-1 ]
C₁₉H₁₆ClFN₂O₅S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3431 - 3434.

23
[ 19415-51-1 ]
4-[(4-chlorophenyl)sulfonyl]-6-(5-fluoro-2-methoxybenzyl)-1,4-diazepan-2,5-dione [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3431 - 3434.

24
[ 19415-51-1 ]
(5-fluoro-2-methoxy-benzyl)-isobutyl-piperidin-4-yl-amine [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2714 - 2718.

25
[ 19415-51-1 ]
[ 878199-31-6 ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 1626 - 1632.
[2]Patent: WO2011/33265,2011,A1 .

26
[ 19415-51-1 ]
6-fluoro-3-iodo-2-phenylchromone [ No CAS ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 1626 - 1632.
[2]Patent: WO2011/33265,2011,A1 .

27
[ 459-60-9 ]
[ 19415-51-1 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 461 - 470.
[2]Chimica Therapeutica,1968,vol. 3,p. 1 - 9.

28
[ 19415-51-1 ]
(E)-3-(5-Fluoro-2-methoxy-phenyl)-acryloyl chloride [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 461 - 470.

29
[ 19415-51-1 ]
(E)-1-(10,10-Dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1,5]dec-4-yl)-3-(5-fluoro-2-methoxy-phenyl)-propenone [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 461 - 470.

30
[ 19415-51-1 ]
[ 157604-02-9 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 461 - 470.

31
[ 19415-51-1 ]
(10,10-Dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1,5]dec-4-yl)-[2-(5-fluoro-2-methoxy-phenyl)-cyclopropyl]-methanone [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 461 - 470.

32
[ 19415-51-1 ]
((1S,5R,7R)-10,10-Dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1,5]dec-4-yl)-[(1R,2R)-2-(5-fluoro-2-methoxy-phenyl)-cyclopropyl]-methanone [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 461 - 470.

33
[ 19415-51-1 ]
[ 82128-85-6 ]

References: [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 770 - 778.

34
[ 19415-51-1 ]
[ 82128-84-5 ]

References: [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 770 - 778.

35
[ 19415-51-1 ]
[ 72955-97-6 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 2001 - 2016.

36
[ 19415-51-1 ]
[ 126209-89-0 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 2001 - 2016.

37
[ 19415-51-1 ]
[ 126209-88-9 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 2001 - 2016.

38
[ 19415-51-1 ]
[ 126209-87-8 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 2001 - 2016.

39
[ 19415-51-1 ]
[ 126209-86-7 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 2001 - 2016.

40
[ 19415-51-1 ]
[ 126247-58-3 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 2001 - 2016.

41
[ 19415-51-1 ]
[ 126209-84-5 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 2001 - 2016.

42
[ 19415-51-1 ]
[ 126209-90-3 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 2001 - 2016.

43
[ 758-16-7 ]
[ 19415-51-1 ]
[ 476198-99-9 ]

Yield	Reaction Conditions	Operation in experiment
28%	With lithium diisopropyl amide; In tetrahydrofuran; n-heptane; at -78 - -5℃; for 1h;	2- (5-FLUORO-2-METHOXYPHENYL)-2-HYDROXY-N, N-DIMETHYLETHANETHIOAMIDE To a solution of lithium DIISOPROPYLAMIDE, 2M in THF/N-HEPTANE (210 mL, 583 mmol) was added THF (100 ML) and the solution cooled to-78C under nitrogen. This was then added dropwise over 1 h to a solution of the <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> (50 g, 0.32 mmol) and N, N-DIMETHYLTHIOFORMAMIDE (34.7 g, 389 mmol) in dry THF (200 mL). This was warmed TO-5C and quenched with water (400 mL). The solution was filtered and washed with diethyl ether, the aqueous layer was extracted with ether (1 L). The combined organic layers were washed with water (500 mL), dried (MgSO4) and the solvent removed in vacuo to give a crystalline suspension in oil. This was triturated in ether and filtered to give a crystalline solid (21.8 g, 28%) ; ON (300 MHz, CDCl3) 7.16- 6.81 (3H, m, ArH), 5.81-5. 75 (1H, m, CHOH), 5.31-5. 22 (1H, m, OH), 4.89 (3H, s, OCH3), 3.50 (3H, s, N (CH3) 2) and 3.08 (3H, s, N (CH3) 2).
28%	With lithium diisopropyl amide; In tetrahydrofuran; n-heptane; at -78 - -5℃; for 1h;	a) 2- (5-FLUORO-2-METHOXYPHENYL)-2-HYDROXY-N, N-DIMETHYLETHANETHIOAMIDE To a solution of lithium diisopropylamide, 2M in THF/N-HEPTANE (210 mL, 583 mmol) was added THF (100 ML) and the solution cooled to-78C under nitrogen. This was then added dropwise over 1 h to a solution of the <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> (50 g, 0.32 mmol) and N, N-DIMETHYITHIOFORMAMIDE (34.7 g, 389 mmol) in dry THF (200 mL). This was warmed to-5C and quenched with water (400 mL). The solution was filtered and washed with diethyl ether, the aqueous layer was extracted with ether (1 L). The combined organic layers were washed with water (500 mL), dried (MGS04) and the solvent removed IRA VACUA to give a crystalline suspension in oil. This was triturated in ether and filtered to give a crystalline solid (21.8 g, 28%) ; 8H (300 MHz, CDC13) 7.16- 6.81 (3H, m, ArH), 5.81-5. 75 (1H, m, CHOH), 5.31-5. 22 (1H, m, OH), 4.89 (3H, s, OCH3), 3.50 (3H, s, N (CH3) 2) and 3.08 (3H, s, N (CH3) 2).

References: [1]Patent: WO2004/43903,2004,A1 .Location in patent: Page 38 - 39.
[2]Patent: WO2004/43904,2004,A1 .Location in patent: Page 37.

44
[ 19415-51-1 ]
[ 426831-32-5 ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium tetrahydroborate; In methanol; at -10 - 20℃; for 0.5h;	To a solution of 2-Methoxy-5-fluorobenzaldehyde (11.093g, 1 equiv.- available from Aldrich Chemical Company) in methanol at-10 C under nitrogen atmosphere was added NaBH4 (7.515g, 2.7 equiv. ) portionwise. The solution was allowed to warm to room temperature and after 30 minutes the reaction solvent was removed under reduced pressure and replaced with dichloromethane. This solution was poured onto ice water and further extracted with dichloromethane. The organic fractions were collected and dried [(MGS04)] and the solvent removed under reduced pressure to give the title compound as an oil (9.794g, [87%).'H] NMR [(300MHZ,] [CDC13)] : [6] 2. [58] (m, 1H), 3.81 (s, 3H), 4.63 (d, 2H, [J =] 6.3 Hz), 6.78 (dd, [1H,] J= 8.9 and 4.3 Hz), 6.94 (td, 1H, J = 8.5 and 3. 1Hz), 7.04 (dd, 1H, J = 8.7 and 3. 1Hz).
87%	With sodium tetrahydroborate; In methanol; at -10 - 20℃; for 0.5h;	To a solution OF 2-METHOXY-5-FLUOROBENZALDEHYDE (11. 093g, 1 equiv.-available from Aldrich Chemical Company) in methanol at-10 C under nitrogen atmosphere was added NaBH4 (7. 515G, 2.7 equiv. ) portionwise. The solution was allowed to warm to room temperature and after 30 minutes the reaction solvent was removed under reduced pressure and replaced with dichloromethane. This solution was poured onto ice water and further extracted with dichloromethane. The organic fractions were collected and dried (MgS04) and the solvent removed under reduced pressure to give the title compound as an oil (9.794g, 87%). H NMR (300MHZ, CDC13) : 6 2.58 (m, 1H), 3.81 (s, 3H), 4.63 (d, 2H, J= 6.3 Hz), 6. 78 (dd, 1H, J= 8.9 and 4.3 Hz), 6.94 (td, 1H, J= 8.5 and 3. 1HZ), 7.04 (dd, 1H, J= 8. 7 AND 3. 1HZ).
87%	With sodium tetrahydroborate; In methanol; at -10 - 20℃; for 0.5h;	To a solution of 2-Methoxy-5-fluorobenzaldehyde (11. 093g, 1 equiv. -available from Aldrich Chemical Company) in methanol at-10 C under nitrogen atmosphere was added NaBH4 (7. 515g, 2.7 equiv.) portionwise : The solution was allowed to warm to room temperature and after 30 minutes the reaction solvent was removed under reduced pressure and replaced with dichloromethane. This solution was poured onto ice water and further extracted with dichloromethane. The organic fractions were collected and dried (MGSO4) and the solvent removed under reduced pressure to give the title compound as an oil (9. 794g, 87%). H NMR (300MHZ, CDC13) : No. 2. 58 (m, 1H), 3. 81 (s, 3H), 4.63 (d, 2H, J= 6.3 Hz), 6.78 (dd, 1H, J= 8.9 and 4.3 Hz), 6.94 (td, 1H, J= 8.5 and 3. 1Hz), 7.04 (dd, 1H, J= 8. 7 AND 3. 1HZ).

87%		To a solution of 2-Methoxy-5-fluorobenzaldehyde (11. 093g, 1 equiv.-available from Aldrich Chemical Company) in methanol at-10 C under nitrogen atmosphere was added NaBH4 (7.515g, 2.7 equiv. ) portionwise. The solution was allowed to warm to room temperature and after 30 minutes the reaction solvent was removed under reduced pressure and replaced with dichloromethane. This solution was poured onto ice water and further extracted with dichloromethane. The organic fractions were collected and dried (MgSO4) and the solvent removed under reduced pressure to give the title compound as an oil (9.794g, 87%).'H NMR (300MHz, CDC13) : S 2.58 (m, 1H), 3.81 (s, 3H), 4.63 (d, 2H, J = 6.3 Hz), 6.78 (dd, 1H, J = 8.9 and 4.3 Hz), 6.94 (td, 1H, J = 8. 5 and 3. lHz), 7.04 (dd, 1H, J= 8. 7 and 3. 1Hz).
52%	With sodium tetrahydroborate; In methanol; at -10 - 20℃; for 0.5h;	(5-Fluoro-2-methoxy-phenyl)-methanol To a solution of <strong>[19415-51-1]2-methoxy-5-fluorobenzaldehyde</strong> (11. 093g, 1 eq, available from Aldrich Chemical Company) in methanol at-10 C under nitrogen atmosphere is added NaBH4 (7. 515g, 2.7 equiv. ) portionwise. The solution is allowed to warm to room temperature and after 30 minutes the reaction solvent is removed under reduced pressure and replaced with dichloromethane. This solution is poured onto ice water and further extracted with dichloromethane. The organic fractions are collected and dried (MgS04) and the solvent removed under reduced pressure to give the title compound as an oil (9.794g, 87%). MW 156.16 ; CsH9F02 ;'H NMR (CDC13) : 2. 58 (m, 1H), 3.81 (s, 3H), 4.63 (d, 2H, 6.3 Hz), 6.78 (dd, 1H, 8. 9 Hz and 4.3 Hz), 6.94 (td, 1H, 8.5 Hz and 3.1 Hz), 7.04 (dd, 1H, 8.7 Hz and 3.1 Hz).
	With sodium tetrahydroborate; In ethanol; at 20℃; for 1h;	This intermediate is synthesised as follows: Add Sodium borohydride (540 mg, 13.95 mmol) in portions to a solution of 5-Fluoro-2- methoxy-benzaldehyde (2.15g, 13.94 mmol) in absolute EtOH (20 ml) and stir at room temperature. After lh, evaporate the solvent, dilute the residue in CH2Cl2 and treat with aqueous 3M HCI. Separate the phases, wash the organic one twice with H2O, dry over Na2S04 and concentrate at vacuum to obtain pure (5-Fluoro-2-methoxy-phenyl)-methanol as white solid. Add aqueous concentrated HBr (15 ml) to a solution of (5-Fluoro-2- methoxy-phenyl)-methanol (1.9g, 12.17 mmol) in CHC13 (10 ml) and stir at room temperature. After 1h, separate the phases, wash the aqueous one with CH2C12, combine organic phases, wash with H2O, dry over Na2SO4 and concentrate at vacuum to obtain a residue. Purify the residue by column chromatography on silica gel eluting with hexane to afford 2-Bromomethyl-4-fluoro-1-methoxy-benzene as white solid.'H-NMR (CDCl3, 200 MHz) : 8 7.06 (dd, J=3.0 and 8.6 Hz, 1H), 6.98 (m, 1H), 6.81 (dd, J= 4.4 and 9.0 Hz, 1H), 4.50 (s, 2H), 3.87 (s, 3H).
	With lithium aluminium tetrahydride; In tetrahydrofuran; at 20 - 60℃;	To a suspension of LiAlH4 (1.2 g, 32 mmol) in dry THF (5 mL) was added the aldehyde (10 mmol) and the mixtures were stirred at room temperature for two hours. Mixtures with aldehydes as starting materials were put aside and the acids were heated at 60 C. overnight. To each mixture was added in consecutive order water (1.2 mL), 2 M aqueous NaOH (1.2 mL), and water (3.6 mL). The precipitate was filtered off and the solvent was removed under reduced pressure to yield the target products as oils. The title compound was prepared starting from <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> and was obtained as a light red oil (94% yield). Fragmenting MS analysis supports the stated structure. Purity 97% (GC). 1H NMR (CDCl3) ?3.28 (s, 3 H), 4.64 (s, 2 H), 6.78 (m, 1 H), 6.93 (m, 1 H), 7.02 (m, 1 H). 13C NMR (CDCl3) ?55.73, 61.34, 110.83 (d, J=8.5 Hz), 114.22 (d, J=22.6Hz), 115.26 (d, J=23.3 Hz), 138.68 (d, J=6.4 Hz), 153.18 (d, J=2.1 Hz), 156.95 (d, J=238.8 Hz).
	With sodium tetrahydroborate; In ethanol; at 0℃; for 1h;	A 100ml four-necked flask was charged with 5.0 g (32.4 mmol) of <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> and 100ml of ethanol, and 1.23 g (32.4 mmol) of sodium borohydride was added thereto with stirring under ice-cooling.. Then, the mixture was stirred for 1 hour and allowed to stand at room temperature overnight.. After concentrating under reduced pressure, 50 ml of ethyl acetate and 50 ml of water were added to the residue, and the mixture was shaken and separated into layers.. The aqueous layer was extracted once again with 50 ml of ethyl acetate.. The ethyl acetate layers were combined, and washed with 50 ml of water followed by 50 ml of saturated brine.. After drying over anhydrous sodium sulfate, the mixture was concentrated under reduced pressure to obtain 5-fluoro-2-methoxybenzyl alcohol.1H-NMR (CDCl3) delta: 3.83 (s, 3H), 4.66 (d, 2H, J= 6.4Hz), 6.77-7.07 (m, 3H).
	With methanol; sodium tetrahydroborate; at 20℃; for 18h;	Step 1: To 42 (1 eq, 17.1 mmol, 2.6 g) in MeOH (68 ml_) at room temperature, added NaBH4 {1.2 eq, 20.5 mmol, 775 mg) and the reaction mixture stirred 18h, then concentrated in vacuo. The crude residue was diluted with ethyl acetate, washed with 1 N aqueous HCI then brine, dried over sodium sulfate, and concentrated in vacuo to give 43 (2.8 g) as a pale yellow oil
		a) Preparation of (5-fluoro-2-methoxy-phenyl)-methanolSodium borohydride (61 mg, 1.62 mmol) is added to a solution of 5-fluoro-2- methoxybenzaldehyde (1.0 g, 6.49 mmol) in MeOH (10 mL). After 1 hour, the reaction is poured in to 1 M aqueous HCI and extracted with DCM. The combined organic phases are dried (Na2SO4) , evaporated and purified by flash chromatography (0-100% EtOAc- isohexanes gradient elution) to afford (5-fluoro-2-methoxy-phenyl)-methanol.

References: [1]Patent: EP1216225,2005,B1 .Location in patent: Page/Page column 39.
[2]Patent: WO2004/18441,2004,A1 .Location in patent: Page 22.
[3]Patent: WO2005/20975,2005,A2 .Location in patent: Page/Page column 126.
[4]Patent: WO2005/20976,2005,A2 .Location in patent: Page/Page column 129.
[5]Patent: WO2005/60949,2005,A2 .Location in patent: Page/Page column 132; 277.
[6]Journal of Organic Chemistry,2013,vol. 78,p. 5955 - 5963.
[7]Patent: WO2005/47272,2005,A1 .Location in patent: Page/Page column 52.
[8]Patent: WO2005/66144,2005,A1 .Location in patent: Page/Page column 42-43.
[9]Patent: US2003/232814,2003,A1 .Location in patent: Page 7.
[10]Patent: EP1460062,2004,A1 .Location in patent: Page 69.
[11]Patent: WO2011/46771,2011,A1 .Location in patent: Page/Page column 148.
[12]European Journal of Organic Chemistry,2017,vol. 2017,p. 996 - 1003.
[13]Patent: WO2006/125593,2006,A1 .Location in patent: Page/Page column 21.

45
[ 19415-51-1 ]
[ 67-64-1 ]
[ 239132-36-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; at 20℃; for 4h;	In water (200 ml) was dissolved sodium hydroxide (3 g), and to the solution was added acetone (80 ml) and then was added dropwise a solution of <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> (10 g) in acetone (25 ml). The reaction solution was stirred at room temperature for 4 hours, and acetone was evaporated under reduced pressure. The residue was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine and concentrated under reduced pressure to give 4-(5-fluoro-2-methoxyphenyl)-3-buten-2-one (13 g). To a solution of 20% sodium ethoxide in ethanol (21.4 g) was added at room temperature diethyl malonate (11.2 g) and then was added little by little 4-(5-fluoro-2-methoxyphenyl)-3-buten-2-one (13 g), and the reaction mixture was stirred at room temperature for 30 minutes, refluxed for 2 hours and cooled. The solvent was evaporated, and to the residue was added water. The aqueous layer was washed with ethyl acetate and concentrated. To the residue was added 2M sodium hydroxide (50 ml), and the mixture was refluxed for 2 hours and cooled. To the mixture was added 2.5M sulfuric acid (50 ml) for 15 minutes, and the mixture was refluxed for 15 minutes and cooled. Precipitated crystals were washed with ethyl acetate to give 5-(5-fluoro-2-methoxyphenyl)cyclohexane-1,3-dione (9.6 g) as pale yellow crystals. mp 160-161 C. 1H-NMR(DMSO-d6) delta: 2.3-2.66 (4H,m), 3.5-3.66 (1H,m), 3.80 (3H,s), 5.29 (1H,s), 6.96-7.17 (3H,m), 11.20 (1H,br).

References: [1]Patent: US6350749,2002,B1 .Location in patent: Page column 136.

46
[ 347-54-6 ]
[ 74-88-4 ]
[ 19415-51-1 ]

References: [1]Patent: EP1216225,2005,B1 .Location in patent: Page/Page column 39.
[2]ChemMedChem,2019,vol. 14,p. 1173 - 1184.

47
[ 19415-51-1 ]
tetrahydro-2-(5-fluoro-2-methoxyphenyl)-5-oxo-3-furancarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium bicarbonate; triethylamine;Zinc chloride; In dichloromethane;	(i) Triethylamine (42 ml) was added with stirring and cooling under an argon atmosphere to a solution containing <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> (23.1 g) [prepared as a white solid, m.p. 41-43 C., by an analogous method to that described in U.S. Pat. Ser. No. 4,367,234] and anhydrous zinc chloride (45 g) in dry dichloromethane (250 ml) at such a rate that the reaction temperature did not exceed 25 C. Stirring was continued for 15 hours. The mixture was acidified to pH 2 with 2M hydrochloric acid and extracted with ethyl acetate (3150 ml). The combined extracts were washed with saturated brine (6100 ml) and extracted with a saturated solution of sodium hydrogen carbonate (460 ml). The combined aqueous extracts were washed with ethyl acetate (50 ml), acidified to pH 2 using concentrated hydrochloric acid, and extracted with ethyl acetate (4100 ml). These extracts were washed with saturated brine (6*50 ml), dried (MgSO4) and evaporated to give tetrahydro-2-(5-fluoro-2-methoxyphenyl)-5-oxo-3-furancarboxylic acid (40 g) as an oily mixture (A) of [ 2,3-cis] and [2,3-trans] diastereomers (39:61 by high pressure liquid chromatographic [HPLC] analysis); NMR: 2.93 (2H, d, J=8 Hz), 3.44 (1H, m), 3.88 (3H, s), 5.82 (1H, d, J=5,7 Hz) and 7.10 (3H, m).
	With hydrogenchloride; sodium bicarbonate; triethylamine;Zinc chloride; In dichloromethane;	(i) Triethylamine (42 ml) was added with stirring and cooling under an argon atmosphere to a solution containing <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> (23.1 g) [prepared as a white solid, m.p. 41-43 C., by an analogous method to that described in U.S. Pat. No. 4367234] and anhydrous zinc chloride (45 g) in dry dichloromethane (250 ml) at such a rate that the reaction temperature did not exceed 25 C. Stirring was continued for 15 hours. The mixture was acidified to pH 2 with 2 M hydrochloric acid and extracted with ethyl acetate (3150 ml). The combined extracts were washed with saturated brine (6100 ml) and extracted with a saturated solution of sodium hydrogen carbonate (460 ml). The combined aqueous extracts were washed with ethyl acetate (50 ml), acidified to pH 2 using concentrated hydrochloric acid, and extracted with ethyl acetate (4100 ml). These extracts were washed with saturated brine (6*50 ml), dried (MgSO4) and evaporated to give tetrahydro-2-(5-fluoro-2-methoxyphenyl)-5-oxo-3-furancarboxylic acid (40 g) as an oily mixture (E) of [2,3-cis] and [2,3-trans] diastereomers (39:61 by high pressure liquid chromatographic [HPLC] analysis); NMR: 2.93 (2H, d, J=8 Hz), 3.44 (1H, m), 3.88 (3H, s), 5.82 (1H, d, J=5, 7 Hz) and 7.10 (3H, m).
	With hydrogenchloride; sodium bicarbonate; triethylamine;Zinc chloride; In dichloromethane;	(i) Triethylamine (42 ml) was added with stirring and cooling under an argon atmosphere to a solution containing <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> (23.1 g) [prepared as a white solid, m.p. 41-43 C., by an analogous method to that described in U.S. Pat. Ser. No. 4,367,234] and anhydrous zinc chloride (45 g) in dry dichloromethane (250 ml) at such a rate that the reaction temperature did not exceed 25 C. Stirring was continued for 15 hours. The mixture was acidified to pH 2 with 2 M hydrochloric acid and extracted with ethyl acetate (3150 ml). The combined extracts were washed with saturated brine (6100 ml) and extracted with a saturated solution of sodium hydrogen carbonate (460 ml). The combined aqueous extracts were washed with ethyl acetate (50 ml), acidified to pH 2 using concentrated hydrochloric acid, and extracted with ethyl acetate (4100 ml). These extracts were washed with saturated brine (6*50 ml), dried (MgSO4) and evaporated to give tetrahydro-2-(5-fluoro-2-methoxyphenyl)-5-oxo-3-furancarboxylic acid (40 g) as an oily mixture (A) of [2,3-cis] and [2,3-trans] diastereomers (39:61 by high pressure liquid chromatographic [HPLC] analysis); NMR: 2.93 (2H, d, J=8 Hz), 3.44 (1H, m), 3.88 (3H, s), 5.82 (1H, d, J=5, 7 Hz) and 7.10 (3H, m).

References: [1]Patent: US4908380,1990,A .
[2]Patent: US4772625,1988,A .
[3]Patent: US4775685,1988,A .

48
[ 19415-51-1 ]
[ 1099-45-2 ]
ethyl (Z)-3-(5'-fluoro-2'-methoxyphenyl)-2-propenoate [ No CAS ]
[ 878662-27-2 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; at 0 - 20℃; for 12h;	To a solution of 5- fluoro-2-methoxybenzaldehyde (4.3 g, 28.0 mmol) in CH2Cl2 (30 mL) at O0C was added portionwise carbethoxymethylenetriphenylphosphorane (10.7 g, 30.1 mmol). The mixture was then warmed to room temperature and stirred for 12 h. The solvent was removed in vacuo and the residue was purified by flash column chromatography (Rf = 0.2, EtOAc/Hexane, 10:90, v:v) to provide the product (6.0 g, 95%) as oil in a 4:1 mixture of tran : cis isomers; 1H NMR (CDCl3, 500 MHz): delta 7.93 (d, J= 16.2 Hz, 0.8 H), 7.33 (dd, J= 3.1, 9.2 Hz, 0.2 H), 7.21 (dd, J= 3.1, 9.2, Hz, 0.8 H), 7.08 (d, J= 12.5 Hz, 0.2 H), 7.03 (dt, J= 3.0, 8.8 Hz, 0.8 H), 6.99 (dt, J= 3.0, 8.8 Hz, 0.2 H), 6.84 (dd, J= 3.1, 8.6 Hz, 0.8 H), 6.79 (dd, J= 3.3, 9.1 Hz, 0.2 H), 6.47 (d, J= 16.2 Hz, 0.8 H), 5.99 (d, J= 12.5 hz, 0.2 H), 4.25 (q, J= 7.1 Hz, 1.6 H), 4.15 (q, J= 7.0 Hz, 0.4 H), 3.86 (s, 2.4 H), 3.81 (s, 0.6 H), 1.34 (t, J= 7.1 Hz, 2.4 H), 1.22 (t, J= 7.0 Hz, 0.6 H). (Rf = 0.4, EtOAc/Hexane, 6:94, v:v)

References: [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 2047 - 2068.
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 1530 - 1539.
[3]Patent: WO2006/25920,2006,A2 .Location in patent: Page/Page column 88; 135-136.

49
[ 19415-51-1 ]
[ 1099-45-2 ]
[ 878662-27-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	In dichloromethane; at 0 - 20℃; for 12h;	To a solution of 5-fluoro-2- methoxybenzaldehyde (4.3 g, 28 mmol) in dry CH2Cl2 (40 mL) at 0C was added carbethoxymethylenetriphenylphosphorane (10.7 g, 30 mmol) portionwise and the reaction was warmed to room temperature for 12 h. The solvent was then removed in vacuo and the residue was purified by flash column chromatography (8% EtOAc in Hexane, Rf = 0.20) to yield the product (4 g, 95%) as an oil.

References: [1]Patent: WO2006/25920,2006,A2 .Location in patent: Page/Page column 46.

50
[ 19415-51-1 ]
[ 4009-98-7 ]
C₁₀H₁₁FO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 13h;Heating / reflux;	Example 3 : rralphaw.s'-2-(ammome1hyl)-5-(5'-fluoro-2'-methoxybenzyl)tetrahydrofuran[0195] S-Fluoro-2-methoxyphenacetaldehyde:; To a suspension of methoxymethyltriphenylphosphonium chloride (10.0 g, 30.0 mmol) in THF (30 mL) under Ar(g) was added NaH (60% in mineral oil, 1.2 g, 30 mmol) and the mixture thus obtained was heated to reflux for 1 h. The orange suspension thus obtained was cooled to O0C and 5- fluoro-2-methoxybenzaldehyde (4.2 g, 26.0 mmol) was added and the reaction was continued for 12 h while warmed to room temperature. The reaction mixture was poured in to a separatory funnel containing ammonium chloride aqueous solution (sat. NH4Cl: H2O=I :1, 100 mL). The organic fraction was extracted with ethyl acetate (3 x 80 mL) and the combined organic layers were washed with brine (60 mL) and dried over sodium sulfate. The solvent was then removed in vacuo and crude product thus obtained was dissolved in acetone (50 mL) and H2SO4 (1 M, 1.5 mL) was added and the mixture thus obtained was heated to reflux for 6 h. It was then cooled to room temperature and the crude product obtained after the removal of the solvent was purified by flash column chromatography (10% ethyl acetate in hexane, Rf = 0.15) to give the product (2.63 g, 66%) as an oil.; [0287] 5-Fluoro~2-methoxyphenylacetaldehyde (2a): To a suspension of methoxymethyltriphenylphosphonium chloride (10.0 g, 30.0 mmol) in THF (30 niL) under Ar was added NaH (60% in mineral oil, 1.2 g, 30 mmol) and then heated to reflux for 1 h. The orange colored suspension was cooled to 0C and <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> (4.2 g, 26.0 mmol) was added and the mixture was stirred for 12 h at room temperature. The reaction mixture was then poured into a separatory funnel containing ammonium chloride aqueous solution (sat. NH4C1/H20, 1:1, v:v, 100 niL). The organic material was extracted with ethyl acetate (3 x 80 mL) and the combined organic layers were washed with brine (60 mL) and dried over Na2SO4. The solvent was then removed in vacuo and the crude product (2a) obtained was dissolved in acetone (50 mL). H2SO4 (1 M, 1.5 mL) was then added and the mixture obtained was heated to reflux for 6 h while stirring. The reaction was then cooled to room temperature and the solvent was removed in vacuo to obtain the crude product that was then purified by flash column chromatography (Rf = 0.15, EtOAc/Hexane, 10:90, v:v) to afford the product (2.63 g, 66%) as an oil: 1H NMR (CDCl3, 500 MHz): delta 9.68 (s, 1 H), 6.97 (dt, J= 3.1, 8.7 Hz, 1 H), 6.89 (dd, J= 3.1, 8.7 Hz, 1 H), 6.83 (dd, J= 4.3, 8.7 Hz, 1 H), 3.80 (s, 3 H), 3.63 (d, J= 1.7 Hz, 2 H).

References: [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 2047 - 2068.
[2]Patent: WO2006/25920,2006,A2 .Location in patent: Page/Page column 43-44; 88.

51
[ 19415-51-1 ]
[ 38203-73-5 ]
[ 878661-05-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	With ammonium chloride; In tetrahydrofuran; at 0℃; for 0.25h;	[0187] l-(2'-Methoxy-5'-fluorophenyl)pent-4-en-l-ol: To a solution of 2-methoxy-5- fluorobenzaldehyde (3.0 g, 19.5 mniol) in THF (20 mL) at O0C was added a solution 1- butenylmagnesium bromide (0.5 M in THF, 45 mL, 22.5 mmol) dropwise for 15 min. Then the reaction mixture was poured to a solution of saturated ammonium chloride (80 mL) in a separatory funnel. The organic fraction was extracted with ethyl acetate (3 x 60 mL) and the combined organic layers were washed with brine (50 mL) and dried over sodium sulfate. The solvent then was removed in vacuo and crude product thus obtained was purified by flash column chromatography (10% EtOAc in hexane, Rf = 0.11) to give the product as an oil (3.27 g, 93%).; [0317] l-(2'-Methoxy-5'-fluorophenyl)pent-4-en-l-ol (12a): To a solution of 2-methoxy- 5-fluorobenzaldehyde (3.0 g, 19.5 mmol) in THF (20 mL) at O0C was added a solution 1- butenylmagnesium bromide (0.5 M in THF, 45 mL, 22.5 mmol) dropwise for 15 min. Then the reaction mixture was poured into a separatory funnel containing solution of saturated ammonium chloride (80 mL). The organics were extracted with EtOAc (3 x 60 mL) and the combined organic layers were washed with brine (50 mL) and dried over Na2SO4. The solvent then was removed in vacuo and crude product was purified by flash column chromatography (Rf = 0.11, EtOAc/Hexane, 10:90, v:v) on silica to afford the product as oil (3.27 g, 93%); 1H NMR (CDCl3, 500 MHz): delta 7.07 (dd, J= 3.1, 9.2 Hz, 1 H), 6.91 (dt, J= 3.1, 9.0 Hz, 1 H), 6.79 (dd, J= 4.2, 8.5 Hz, 1 H), 5.85 (m, 1 H), 5.04 (d, J= 18.0 Hz, 1 H), 4.97 (d, J= 13.5 Hz, 1 H), 4.90 (t, J= 6.3 Hz, 1 H), 3.83 (s, 3 H), 2.42 (bs, 1 H), 2.23-2.13 (m, 2 H), 1.84 (q, J= 7.7 Hz, 2 H).

References: [1]Patent: WO2006/25920,2006,A2 .Location in patent: Page/Page column 41; 94.

52
[ 19415-51-1 ]
[ 86608-70-0 ]
[ 878662-34-1 ]
(E)-1-(5'-fluoro-2'-methoxyphenyl)-4,4-ethylenedioxy-1-butene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 13h;Heating / reflux;	[0312] l-(5'-Fluoro-2'-methoxyphenyl)-4-ethylenedioxy-l-butene (7): To a suspension of 2-(l,3-dioxolan-2-yl)ethyltriphenylphosphonium bromide (5.0 g, 11.3 mmol) in THF (30 niL) under Ar was added NaH (60% in mineral oil, 0.48 g, 11.3 mmol). The reaction was heated to reflux for 1 h. The resulting orange colored suspension was cooled to 0C and 5- fluoro-2-methoxybenzaldehyde (1.54 g, 10.0 mmol) was added and the reaction was stirred for 12 h at room temperature. The mixture was poured to a separatory funnel containing ammonium chloride aqueous solution (sat. NH4C1/H2O = 1:1, v:v, 30 mL). The organics were extracted with EtOAc (3 x 80 mL) and the combined organic layers were washed with brine (60 mL) and dried over Na2SO4. The solvent was removed in vacuo and product was purified by flash column chromatography (Rf = 0.15, EtOAc/Hexane, 7:93, v:v) to result in the product (2.63 g, 66%) as a mixture of CM and trans (cis:trans = 4: 1): 1H NMR (the major isomer): (CDCl3, 500 MHz): delta 7.08 (dd, J= 3.1, 8.7 Hz, 1 H), 6.93 (dt, J= 3.1, 8.7 Hz, 1 H), 6.78 (dd, J= 4.3, 8.7 Hz, 1 H), 6.63 (d, J= 11.9 Hz, 1 H), 5.83 (td, J= 7.3 Hz, 11.9 Hz, 1 H), 4.99 (t, J= 4.6 Hz, 1 H), 4.02-3.99 (m, 2 H), 3.90-3.87 (m, 2 H), 3.80 (s, 3 H), 2.64-2.62 (m, 2 H).; [0470] l-(5'~Fluoro-2'-methoxyphenyl)-4-ethylenedioxy-l-butene (5): To a suspension of 2-(l,3-dioxolan-2-yl)ethyltrirhohenylrhohosrhohonium bromide (5.0 g, 11.3 mmol) in THF (30 mL) under an atmosphere of Ar was added NaH (60% in mineral oil, 0.48 g, 11.3 mmol) and the mixture obtained was heated to reflux for 1 h. The orange suspension obtained was cooled to 0 C and <strong>[19415-51-1]5-fluoro-2-methoxybenzaldehyde</strong> (1.54 g, 10.0 mmol) was added and the reaction was warmed to room temperature and continued with stirring for 12 h. The reaction mixture was poured to a separatory funnel containing ammonium chloride aqueous solution (sat. NH4C1/H2O 50:50, v:v, 50 mL). The organics were extracted with EtOAc (3 x 80 mL) and the combined organic layers were washed with brine (60 mL) and dried over sodium sulfate. The solvent was then removed in vacuo and the crude product obtained was purified by flash column chromatography (EtOAc/hexane, 7:93, v:v, Rf = 0.15) to give the product (2.63 g, 66%) as a 4:1 mixture of cis and trans diastereomers: 1H NMR (major isomer): (CDCl3, 500 MHz): delta 7.08 (dd, J= 3.1, 8.7 Hz, 1 H), 6.93 (dt, J= 3.1, 8.7 Hz, 1 H), 6.78 (dd, J= 4.3, 8.7 Hz, 1 H), 6.63 (d, J= 11.9 Hz, 1 H), 5.83 (td, J= 7.3 Hz, 11.9 Hz, 1 H), 4.99 (t, J= 4.6 Hz, 1 H), 4.02-3.99 (m, 2 H), 3.9-3.87 (m, 2 H), 3.8 (s, 3 H), 2.64-2.62 (m, 2 H).

53
[ 1136479-97-4 ]
[ 19415-51-1 ]
[ 1136479-96-3 ]

Yield	Reaction Conditions	Operation in experiment
7%		N6-Pyridin-3-ylmethyl-quinoline-2,6-diamine (150 mg, 0.6 mmol) was dissolved in 10 mL dichloromethane. 5-Fluoro-2-methoxybenzaldehyde (111 mg, 0.72 mmol) and acetic acid (72 mg, 1.2 mmol) were added. The reaction mixture was stirred at 40 C. for 3 h. Sodium triacetoxy borohydride (254 mg, 1.2 mmol) was added and stirring was continued at room temperature overnight. The reaction mixture was quenched by addition of 20 mL sat. sodiumbicarbonate solution. The mixture was extracted three times with dichloromethane (20 mL each). The organic phases ware pooled, dried with sodium sulfate, filtered and evaporated. The residue purified by flash chromatography on silica gel (dichloromethane/methanol 100:0?90:10 gradient). The title compound was obtained as a yellow gum (17 mg, 7%), MS: m/e=389.3 (M+H+).

References: [1]Patent: US2009/88451,2009,A1 .Location in patent: Page/Page column 21-22.

54
[ 19415-51-1 ]
[ 7103-09-5 ]
[ 878661-05-3 ]

References: [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 2047 - 2068.

Historical Records

Technical Information

• Alkyl Halide Occurrence • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Chaykovsky Reaction • Corey-Fuchs Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • Grignard Reaction • Hantzsch Dihydropyridine Synthesis • Henry Nitroaldol Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Julia-Kocienski Olefination • Knoevenagel Condensation • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mukaiyama Aldol Reaction • Nomenclature of Ethers • Nozaki-Hiyama-Kishi Reaction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Preparation of Ethers • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Ethers • Reformatsky Reaction • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Stetter Reaction • Stobbe Condensation • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

Related Functional Groups of
[ 19415-51-1 ]

Fluorinated Building Blocks

A320303 [450-83-9]

4-Fluoro-2-methoxybenzaldehyde

Similarity: 0.98

A392294 [202857-89-4]

2-(Benzyloxy)-4-fluorobenzaldehyde

Similarity: 0.93

A214923 [347-54-6]

5-Fluoro-2-hydroxybenzaldehyde

Similarity: 0.90

A292427 [394-04-7]

5-Fluoro-2-methoxybenzoic acid

Similarity: 0.89

A301097 [51788-80-8]

1-(4-Fluoro-2-methoxyphenyl)ethanone

Similarity: 0.89

Aryls

A320303 [450-83-9]

4-Fluoro-2-methoxybenzaldehyde

Similarity: 0.98

A392294 [202857-89-4]

2-(Benzyloxy)-4-fluorobenzaldehyde

Similarity: 0.93

A214923 [347-54-6]

5-Fluoro-2-hydroxybenzaldehyde

Similarity: 0.90

A292427 [394-04-7]

5-Fluoro-2-methoxybenzoic acid

Similarity: 0.89

A301097 [51788-80-8]

1-(4-Fluoro-2-methoxyphenyl)ethanone

Similarity: 0.89

Aldehydes

A320303 [450-83-9]

4-Fluoro-2-methoxybenzaldehyde

Similarity: 0.98

A392294 [202857-89-4]

2-(Benzyloxy)-4-fluorobenzaldehyde

Similarity: 0.93

A214923 [347-54-6]

5-Fluoro-2-hydroxybenzaldehyde

Similarity: 0.90

A113695 [66742-57-2]

4-((3-Fluorobenzyl)oxy)benzaldehyde

Similarity: 0.89

A136939 [699016-24-5]

3-Fluoro-5-methoxybenzaldehyde

Similarity: 0.88

Ethers

A320303 [450-83-9]

4-Fluoro-2-methoxybenzaldehyde

Similarity: 0.98

A392294 [202857-89-4]

2-(Benzyloxy)-4-fluorobenzaldehyde

Similarity: 0.93

A292427 [394-04-7]

5-Fluoro-2-methoxybenzoic acid

Similarity: 0.89

A301097 [51788-80-8]

1-(4-Fluoro-2-methoxyphenyl)ethanone

Similarity: 0.89

A113695 [66742-57-2]

4-((3-Fluorobenzyl)oxy)benzaldehyde

Similarity: 0.89

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CAS No.: 19415-51-1

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[ 19415-51-1 ]

Fluorinated Building Blocks

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CAS No.: 19415-51-1

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Alternative Products

Product Details of [ 19415-51-1 ]

Safety of [ 19415-51-1 ]

Computational Chemistry of [ 19415-51-1 ] Show Less

Physicochemical Properties

Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 19415-51-1 ]

[ 19415-51-1 ] Synthesis Path-Downstream 1~54

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of [ 19415-51-1 ]

Fluorinated Building Blocks

Aryls

Aldehydes

Ethers

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Molarity Calculator

Total Compounds Calculator

Dissolution Calculator

Related Functional Groups of
[ 19415-51-1 ]