145691-59-4|(3,5-Dibromophenyl)methanol| Ambeed

CAS No. :	145691-59-4
Formula :	C₇H₆Br₂O
M.W :	265.93
SMILES Code :	OCC1=CC(Br)=CC(Br)=C1
MDL No. :	MFCD01632143
InChI Key :	ZQNSHKZQTZSNTB-UHFFFAOYSA-N
Pubchem ID :	7009423

Safety of [ 145691-59-4 ]

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

Computational Chemistry of [ 145691-59-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.14
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	1.0
Molar Refractivity	47.97
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	20.23 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.37
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	3.03
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.55
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.	3.03
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	3.03
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.8

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.78
Solubility	0.0446 mg/ml ; 0.000168 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.	-3.12
Solubility	0.202 mg/ml ; 0.000758 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	-3.93
Solubility	0.031 mg/ml ; 0.000117 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	Yes
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.	-5.77 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<0.0
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)	1.36

Application In Synthesis of [ 145691-59-4 ]

* 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.

Downstream synthetic route of [ 145691-59-4 ]

[ 145691-59-4 ] Synthesis Path-Downstream 1~54

1
[ 56908-88-4 ]
[ 145691-59-4 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1926,vol. 45,p. 303.

2
[ 56990-02-4 ]
[ 145691-59-4 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 1h;	Example 15 [4-[3,5-Bis-[(4-trifluoromethylphenyl)ethynyl]benzyloxy]-2-methylphenoxy]acetic acid 3,5-Dibromobenzaldehyde (1.7 g, 6.3 mmol) was dissolved in methanol (100 mL) and sodium borohydride (0.250 g, 6.3 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 0° C. and then at 20° C. for another 0.5 h. The reaction mixture was concentrated in vacuo, diluted with brine (250 mL), acidified with hydrochloric acid and extracted with dichloromethane (3*50 mL). Evaporation of the organic solution gave 3,5-dibromo-benzyl alcohol as a white crystalline compound. Yield: 1.4 g (84percent). RF (SiO2, hexanes/ethyl acetate 9:1) 0.25. 1H NMR spectrum (300 MHz, CDCl3, A) 7.59 (d, J=1.5 Hz, 1H); 7.47 (d, J=1.5 Hz, 2H); 4.36 (s, 2H); 1.55 (s, 1H).
84%	With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 1h;	Example 15; [4-[3,5-Bis-[(4-trifluoromethylphenyl)ethynyl]benzyloxy]-2-methylphenoxy]acetic acid; 3,5-Dibromobenzaldehyde (1.7 g, 6.3 mmol) was dissolved in methanol (100 mL) and sodium borohydride (0.250 g, 6.3 mmol) was added at 0 °C. The reaction mixture was stirred for 0.5 h at 0 °C and then at 20 °C for another 0.5 h. The reaction mixture was con- centrated in vacuo, diluted with brine (250 mL), acidified with hydrochloric acid and extracted with dichloromethane (3 x 50 mL). Evaporation of the organic solution gave 3,5-dibromo- benzyl alcohol as a white crystalline compound. Yield: 1.4 g (84 percent). RF (Si02, hexanes/ethyl acetate 9:1) 0.25. 1H NMR spectrum (300 MHz, CDCl3, No.H) : 7.59 (d, J=1.5 Hz, 1 H) ; 7.47 (d, J=1.5 Hz, 2 H); 4.36 (s, 2 H); 1.55 (s, 1 H).
	With sodium borohydrid; In methanol;	PREPARATION 9 3,5-Dibromobenzyl alcohol Sodium borohydride (0.75 g) was added portionwise to a stirred suspension of 3,5-dibromobenzaldehyde (10.46 g) in methanol (50 ml) at 0° C. The mixture was stirred at 0° C. for 30 minutes, allowed to warm to room temperature and then its pH was adjusted to 2 using concentrated hydrochloric acid. Evaporation under vacuum provided a residue which was partitioned between ethyl acetate and water. The organic phase was washed with water, dried (MgSO4), then evaporated under vacuum to furnish the title compound as a solid (10.0 g), m.p. 103°-104° C. Found: C,31.98; H,2.23. C7 H6 Br2 O requires C,31.61; H,2.77percent.

Example 1.1.76: (3-isopropyl-5-(methylsulfonylmethyl)phenyl)methanamine; To stirring solution of 5.0 g (18.9 mmol) of 3,5-dibromobenzaldehyde in 30 mL of MeOH and 25 mL of THF at 0 0C was added 819 mg of NaBH4 in 3 portions. The yellow solution was stirred at 0 0C for 30 min. and then concentrated. Water and EtOAc were added, and 1 N HCl was added to a pH = 7. The organic layer was washed with 25 mL of brine, dried over Na2SO4, filtered, and concentrated. (3,5-dibromophenyl)methanol was used in the next reaction without further purification.

References: [1]Chemistry - A European Journal,2012,vol. 18,p. 7473 - 7485.
[2]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.
[3]Organic Letters,2004,vol. 6,p. 2765 - 2767.
[4]Patent: US2009/209588,2009,A1 .Location in patent: Page/Page column 25.
[5]Patent: WO2005/105726,2005,A1 .Location in patent: Page/Page column 62.
[6]Chemical Communications,2004,p. 1582 - 1583.
[7]Patent: US5457118,1995,A .
[8]Patent: WO2009/42694,2009,A1 .Location in patent: Page/Page column 114.
[9]Journal of Polymer Science, Part A: Polymer Chemistry,2014,vol. 52,p. 707 - 718.

3
[ 145691-59-4 ]
[ 140-88-5 ]
(E)-3-[3-((E)-2-Ethoxycarbonyl-vinyl)-5-hydroxymethyl-phenyl]-acrylic acid ethyl ester [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

4
[ 56990-02-4 ]
heptyltriphenylphosphonium iodide [ No CAS ]
[ 145691-59-4 ]
[ 193408-02-5 ]

References: [1]Australian Journal of Chemistry,1997,vol. 50,p. 425 - 434.

5
[ 110-87-2 ]
[ 145691-59-4 ]
[ 225932-10-5 ]

References: [1]European Journal of Organic Chemistry,2009,p. 2953 - 2955.
[2]Macromolecules,2012,vol. 45,p. 5418 - 5426.
[3]Synthesis,1999,p. 683 - 687.

6
[ 109-87-5 ]
[ 145691-59-4 ]
[ 225932-11-6 ]

References: [1]Synthesis,1999,p. 683 - 687.

7
[ 111-25-1 ]
[ 145691-59-4 ]
[ 225932-12-7 ]

References: [1]Synthesis,1999,p. 683 - 687.

8
[ 56908-88-4 ]
KOH-solution [ No CAS ]
[ 145691-59-4 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1926,vol. 45,p. 303.

9
[ 618-58-6 ]
[ 145691-59-4 ]

Yield	Reaction Conditions	Operation in experiment
94%	With dimethylsulfide borane complex; In tetrahydrofuran; at 0 - 20℃;	Step 1 : To a stirred solution of 3,5-dibromobenzoic acid (2 g, 7.168 mmol) in tetrahydrofuran (20 mL) was added borane dimethylsulfide (3.4 mL, 35.842 mmol, 5 eq.) at 0 °C, and the reaction mixture was stirred at room temperature for overnight. The reaction mixture was quenched with methanol at 0 °C and concentrated under vacuo to obtain (3,5- dibromophenyl)methanol as an off white solid (1.8 g, 94percent). H NMR (400 MHz, DMSO-d6) delta ppm 4.47 (d, J = 6 Hz, 2H), 5.39 (t, J = 6 Hz, 1 H), 7.49 (s, 2H), 7.65 (s, 1 H).
	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere;	General procedure: 3,5-Di-t-butylbenzoic acid (5.00 g, 0.021 mol) was dissolved in anhydrous THF (250 mL) under argon atmosphere and the solution cooled to 0 °C. Lithium aluminum hydride (1.62 g, 0.043 mol) was added in small portions and the solution stirred at room temperature overnight. The reaction was quenched with water, Et2O (100 mL) was added and the mixture acidified with concentrated HCl solution until the solid residue was dissolved. The medium was extracted with Et2O and the organic phase dried over MgSO4, filtered and concentrated to yield 4.31g of 5a.

References: [1]Patent: WO2017/46739,2017,A1 .Location in patent: Page/Page column 60.
[2]Patent: JP2005/120047,2005,A .Location in patent: Page/Page column 165.
[3]Synlett,2002,p. 251 - 254.
[4]European Journal of Medicinal Chemistry,2011,vol. 46,p. 4227 - 4237.

10
[ 145691-59-4 ]
[ 56990-02-4 ]

References: [1]Synlett,2002,p. 251 - 254.

11
[ 2510-23-8 ]
[ 145691-59-4 ]
[ 752224-60-5 ]

References: [1]Organic Letters,2004,vol. 6,p. 2765 - 2767.

12
[ 13154-24-0 ]
[ 145691-59-4 ]
[ 757248-89-8 ]

References: [1]Tetrahedron,2006,vol. 62,p. 2060 - 2073.
[2]Chemical Communications,2004,p. 1582 - 1583.

13
[ 145691-59-4 ]
[ 89343-06-6 ]
[ 945867-08-3 ]

References: [1]European Journal of Organic Chemistry,2007,p. 2700 - 2712.

14
[ 145691-59-4 ]
[ 56908-88-4 ]

Yield	Reaction Conditions	Operation in experiment
2.5 g	With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 1h;	General procedure: 3,5-Di-t-butylbenzoic acid (5.00 g, 0.021 mol) was dissolved in anhydrous THF (250 mL) under argon atmosphere and the solution cooled to 0 C. Lithium aluminum hydride (1.62 g, 0.043 mol) was added in small portions and the solution stirred at room temperature overnight. The reaction was quenched with water, Et2O (100 mL) was added and the mixture acidified with concentrated HCl solution until the solid residue was dissolved. The medium was extracted with Et2O and the organic phase dried over MgSO4, filtered and concentrated to yield 4.31g of 5a. 1H NMR delta (CDCl3) 1.34 (s, 18H, di-t-butyl), 4.70 (s, 2H, PhCH2OH), 7.23 (d, 2H, J = 1.8 Hz, 2-CH and 6-CH), 7.38 (t, 1H, J = 1.8 Hz, 4-CH). Crude alcohol 5a (4.25 g) was dissolved in anhydrous CH2Cl2 (500 mL) and cooled at 0 C. Triphenylphosphine (10.23 g, 0.039 mol) and carbon tetrabromide (12.93 g, 0.039 mol) were added and the mixture was stirred at room temperature for 1 h. The reaction mixture was quenched with water and extracted with CH2Cl2. The organic phase was dried over MgSO4, filtered and concentrated. The product was purified by flash chromatography on silica gel with hexanes to yield 4.62 g (86%) of bromide 5b.

References: [1]Chemistry - A European Journal,2012,vol. 18,p. 7473 - 7485.
[2]European Journal of Organic Chemistry,2007,p. 2700 - 2712.
[3]Journal of Medicinal Chemistry,2015,vol. 58,p. 1215 - 1227.
[4]European Journal of Medicinal Chemistry,2011,vol. 46,p. 4227 - 4237.
[5]Chemical Communications,2019,vol. 55,p. 7962 - 7965.

15
[ 145691-59-4 ]
[ 945867-05-0 ]

References: [1]European Journal of Organic Chemistry,2007,p. 2700 - 2712.

16
[ 145691-59-4 ]
[ 945867-06-1 ]

References: [1]European Journal of Organic Chemistry,2007,p. 2700 - 2712.

17
[ 145691-59-4 ]
[ 945867-07-2 ]

References: [1]European Journal of Organic Chemistry,2007,p. 2700 - 2712.

18
[ 145691-59-4 ]
[ 945867-09-4 ]

References: [1]European Journal of Organic Chemistry,2007,p. 2700 - 2712.

19
[ 145691-59-4 ]
[ 945867-10-7 ]

References: [1]European Journal of Organic Chemistry,2007,p. 2700 - 2712.

20
[ 145691-59-4 ]
[ 945867-03-8 ]

References: [1]European Journal of Organic Chemistry,2007,p. 2700 - 2712.

21
[ 145691-59-4 ]
[ 945867-04-9 ]

References: [1]European Journal of Organic Chemistry,2007,p. 2700 - 2712.

22
[ 145691-59-4 ]
[ 757248-90-1 ]

References: [1]Tetrahedron,2006,vol. 62,p. 2060 - 2073.
[2]Chemical Communications,2004,p. 1582 - 1583.

23
[ 145691-59-4 ]
[ 752224-61-6 ]

References: [1]Organic Letters,2004,vol. 6,p. 2765 - 2767.

24
[ 145691-59-4 ]
[ 752224-64-9 ]

References: [1]Organic Letters,2004,vol. 6,p. 2765 - 2767.

25
[ 145691-59-4 ]
aminoacetic acid 3,5-bis-(pyridin-3-ylethynyl)benzyl ester trifluoroacetate [ No CAS ]

References: [1]Organic Letters,2004,vol. 6,p. 2765 - 2767.

26
[ 145691-59-4 ]
3-bromo-5-(3-hydroxy-prop-1-ynyl)-benzaldehyde [ No CAS ]

References: [1]Synlett,2002,p. 251 - 254.

27
[ 145691-59-4 ]
[ 422569-56-0 ]

References: [1]Synlett,2002,p. 251 - 254.

28
[ 145691-59-4 ]
3-[3-(3-hydroxy-prop-1-ynyl)-5-vinyl-phenyl]-prop-2-yn-1-ol [ No CAS ]

References: [1]Synlett,2002,p. 251 - 254.

29
[ 145691-59-4 ]
1,3-bis-[3-(<i>tert</i>-butyl-dimethyl-silanyloxy)-prop-1-ynyl]-5-vinyl-benzene [ No CAS ]

References: [1]Synlett,2002,p. 251 - 254.

30
[ 145691-59-4 ]
3,5-bis-[3-(<i>tert</i>-butyl-dimethyl-silanyloxy)-prop-1-ynyl]-benzaldehyde [ No CAS ]

References: [1]Synlett,2002,p. 251 - 254.

31
[ 145691-59-4 ]
[ 225932-18-3 ]

References: [1]Synthesis,1999,p. 683 - 687.

32
[ 145691-59-4 ]
[ 223463-19-2 ]

References: [1]Synthesis,1999,p. 683 - 687.

33
[ 145691-59-4 ]
[ 225932-17-2 ]

References: [1]Synthesis,1999,p. 683 - 687.

34
[ 145691-59-4 ]
[ 225932-21-8 ]

References: [1]Synthesis,1999,p. 683 - 687.

35
[ 145691-59-4 ]
[ 225932-22-9 ]

References: [1]Synthesis,1999,p. 683 - 687.

36
[ 145691-59-4 ]
[ 225932-20-7 ]

References: [1]Synthesis,1999,p. 683 - 687.

37
[ 145691-59-4 ]
[ 225932-25-2 ]

References: [1]Synthesis,1999,p. 683 - 687.

38
[ 145691-59-4 ]
[ 225932-24-1 ]

References: [1]Synthesis,1999,p. 683 - 687.

39
[ 145691-59-4 ]
[ 225797-84-2 ]

References: [1]Synthesis,1999,p. 683 - 687.

40
[ 626-39-1 ]
[ 145691-59-4 ]

References: [1]Australian Journal of Chemistry,1997,vol. 50,p. 425 - 434.
[2]Journal of Polymer Science, Part A: Polymer Chemistry,2014,vol. 52,p. 707 - 718.

41
[ 145691-59-4 ]
[ 145692-05-3 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

42
[ 145691-59-4 ]
[ 145691-84-5 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

43
[ 145691-59-4 ]
ethyl 3-(2-ethoxycarbonylethenyl)-5-(1-imidazolylmethyl)cinnamate [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

44
[ 145691-59-4 ]
(E)-3-[3-((E)-2-Ethoxycarbonyl-vinyl)-5-methanesulfonyloxymethyl-phenyl]-acrylic acid ethyl ester [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

45
[ 145691-59-4 ]
[ 145691-80-1 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

46
[ 145691-59-4 ]
[ 145691-91-4 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

47
[ 145691-59-4 ]
3-[3-(2-Benzenesulfonylamino-ethyl)-5-imidazol-1-ylmethyl-phenyl]-propionic acid [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

48
[ 145691-59-4 ]
3-{3-[2-(4-Chlorophenylsulphonylamino)ethyl]-5-(1-imidazolylmethyl)phenyl}propanoic acid [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

49
[ 145691-59-4 ]
[ 145691-02-7 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

50
[ 145691-59-4 ]
[ 145691-04-9 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3442 - 3452.

51
[ 145691-59-4 ]
[ 18162-48-6 ]
[ 149428-34-2 ]

Yield	Reaction Conditions	Operation in experiment
	With 1H-imidazole; In DMF (N,N-dimethyl-formamide);	tert-Butyldimethylsilyl 3,5-dibromobenzyl ether. A mixture of 3,5-dibromobenzyl alcohol (9.77 g, 36.74 mmol), tert-butyldimethylchlorosilane (6.80 g, 45.1 mmol) and imidazole (6.08 g, 89.3 mmol) in DMF (100 mL) was stirred under argon over night. The reaction mixture was diluted with ether, washed with water three times, dried over magnesium sulfate, and concentrated under vacuum to provide the title compound. 1H NMR (400 MHz, CDCl3) delta 7.58 (s, 1H), 7.39 (s, 2H), 4.62 (s, 2H), 0.95 (s, 9H), 0.05 (s, 6H).
	With 1H-imidazole; In N,N-dimethyl-formamide; at 20℃;	Step 1 tert-Butyl-(3,5-dibromobenzyloxy)dimethyl silane (21A) A solution of 3,5-dibromobenzyl alcohol (16.5 g, 62.0 mmol), imidazole (10.8 g, 158.7 mmol) and tert-butyldimethylchlorosilane (11.5 g, 76.3 mmol) in DMF (100 mL) was stirred over weekend at ambient temperature. The solvent was removed under vacuum. The residue was dissolved in diethyl ether and washed with water four times and brine once. The organic phase was dried over magnesium sulfate and concentrated to give 21A.

References: [1]Journal of Polymer Science, Part A: Polymer Chemistry,2014,vol. 52,p. 707 - 718.
[2]Patent: US2003/229079,2003,A1 .Location in patent: Page 33-34.
[3]Patent: US2005/10048,2005,A1 .Location in patent: Page/Page column 57.

52
[ 145691-59-4 ]
[ 74337-30-7 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; In DMF (N,N-dimethyl-formamide); for 0.5h;	3, [5-DIBROMOBENZYL ALCOHOL] (9.8 g, 36.9 [MMOL)] is dissolved in DMF (100 ml) and, while stirring, thionyl chloride (5 [ML)] is slowly added dropwise. [AFTER30 M IN,] the reaction mixture is concentrated in vacuo and the residue is taken up in EA (150 [ML). FORWORKUP,] the organic phase is washed with ice-water (50 ml) and then with half-saturated aqueous NaCi solution (50 [ML).] The organic phase is dried over [MGS04,] filtered and concentrated in vacuo. The title compound (10.4 g) is obtained as a yellow solid. TLC [PE/EA (95: [05)], RF=] 0.69.
		1,3-Dibromo-benzyl alcohol (1) (20 g, 75.2 mmol) was dissolved in anhydrous DCM (200 mL) in a dried flask under nitrogen. The reaction mixture was cooled to 0 °C and stirred under nitrogen atmosphere. DIPEA (25.8 mL, 150.4 mmol) was added drop wise to the above solution, after 10 minutes of stirring at 0 °C, mesyl cholride (8.7 mL, 112.8 mmol) was added drop-wise to the above reaction mixture. Finally, the reaction mixture was allowed to stir at RT for 2 hrs. Reaction mixture was diluted with DCM, washed with water (100 mL) followed by NaHC03 solution and brine, dried over anhydrous Na2S04, filtered and evaporated to dryness to give 21 gm of crude product (2) as a brown liquid which was carried forward to the next step as such.
	With methanesulfonyl chloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 26℃; for 2h;Inert atmosphere;	(3,5-Dibromophenyl)methanol (10 g, 37.60 mmol, 1 eq) was dissolved in anhydrous DCM (100 mL) in a dried flask under nitrogen. The reaction mixture was cooled to 0°C and stirred under nitrogen atmosphere. DIEA (9.72 g, 75.21 mmol, 13.10 mL, 2 eq) was added drop wise to the above solution, after 10 minutes of stirring at 0°C, MsCl (6.46 g, 56.41 mmol, 4.37 mL, 1.5 eq) was added drop-wise to the above reaction mixture. Finally, the reaction mixture was allowed to stir at 26°C for 2hrs. TLC (Petroleum ehter : EtOAc = 5:1, uv & stained by KMnO4) showed starting alcohol was consumed up and two new spots were formed. Reaction mixture was washed with water (80 mL) followed by NaHCO3 (80 mL) solution and brine (80 mL), dried over anhydrous Na2SO4, filtered and evaporated to dryness to give the desired product as a brown liquid (12.11g). The above liquid was used directly for the next step without further purification. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 3.04 (s, 3 H) 4.49 (s, 2 H) 5.16 (s, 2 H) 7.48 (d, J=1.76 Hz, 2 H) 7.50 (d, J=1.76 Hz, 2 H) 7.63 (t, J=1.76 Hz, 1 H) 7.70 (t, J=1.76 Hz, 1 H).

References: [1]Patent: WO2004/12731,2004,A1 .Location in patent: Page/Page column 19.
[2]Patent: WO2014/15054,2014,A1 .Location in patent: Page/Page column 198.
[3]Patent: WO2018/132268,2018,A1 .Location in patent: Page/Page column 90.

53
[ 145691-59-4 ]
[ 317319-10-1 ]
[ 868835-06-7 ]

Yield	Reaction Conditions	Operation in experiment
56%	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; toluene; at 0 - 20℃;	The above benzyl alcohol (0.26 g, 1.0 mmol) and methyl (4-hydroxy-2-methylphenoxy)acetate (0.30 g, 1.5 mmol) and triphenylphosphine (0.50 g, 1.85 mmol) were dissolved in a mixture of anhydrous toluene (3-mL) and tetrahydrofuran (1 mL) and the mixture was cooled to 0° C. Diisopropyl azodicarboxylate (0.22 g, 1.2 mmol) was added dropwise under nitrogen. The reaction mixture was stirred for 12 h at ambient temperature and the solvents were evaporated in vacuo. Column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 98:2-90:10) gave methyl [4-(3,5-dibromo)benzyloxy]-2-methylphenoxy]acetate. Yield: 0.25 g (56percent). RF (SiO2, hexanes/ethyl acetate 8:2) 0.45. 1H NMR spectrum (300 MHz, CDCl3, deltaH): 7.61 (s, 1H); 7.48 (s, 2H); 6.80 (s, 1H); 6.67 (s, 2H); 4.92 (s, 2H); 4.60 (s, 2H); 3.80 (s, 3H); 2.28 (s, 3H).
56%	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; toluene; at 0 - 20℃; for 12h;	The above benzyl alcohol (0.26 g, 1.0 mmol) and methyl (4-hydroxy-2-methyl- phenoxy) acetate (0.30 g, 1.5 mmol) and triphenylphosphine (0.50 g, 1.85 mmol) were dis- solved in a mixture of anhydrous toluene (3 mL) and tetrahydrofuran (1 mL) and the mixture was cooled to 0 °C. Diisopropyl azodicarboxylate (0.22 g, 1.2 mmol) was added dropwise under nitrogen. The reaction mixture was stirred for 12 h at ambient temperature and the sol- vents were evaporated in vacuo. Column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 98: 2-90:10) gave methyl [4-(3,5-dibromo)benzyloxy]-2-methylphenoxy]acetate. Yield: 0.25 g (56 percent). RF (Si02, hexanes/ethyl acetate 8: 2) 0.45. 1H NMR spectrum (300 MHz, CDCI3, No.H) : 7.61 (s, 1 H) ; 7.48 (s, 2 H) ; 6.80 (s, 1 H) ; 6.67 (s, 2H) ; 4.92 (s, 2 H) ; 4.60 (s, 2 H) ; 3.80 (s, 3 H) ; 2.28 (s, 3 H).

References: [1]Patent: US2009/209588,2009,A1 .Location in patent: Page/Page column 25-26.
[2]Patent: WO2005/105726,2005,A1 .Location in patent: Page/Page column 62.

Yield	Reaction Conditions	Operation in experiment
		STR13 Preparation of 3,5-dibromobenzylalcohol 1.14G(30 mM) of sodium borohydride was added slowly to a suspension of 3,5-dibromobenzaldehyde (7.92G; 30 mM), from step (a), in 50 mL of methanol at 0° under nitrogen. After stirring 30 mins., the reaction mixture was diluted with 150 mL of ethyl acetate and washed with 5*50 mL of saturated sodium chloride solution, dried over anhydrous magnesium sulfate. Solvent removal afforded a crude product, which was dissolved in minimum amount of CH2 Cl2 and applied on silica gel. Elution with 1:2 mixture of EtOAc:hexane gave 7.2G of the desired alcohol as white solid.

Historical Records

Technical Information

• Alkyl Halide Occurrence • Appel Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chugaev Reaction • Corey-Kim Oxidation • Dess-Martin Oxidation • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Jones Oxidation • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Martin's Sulfurane Dehydrating Reagent • Mitsunobu Reaction • Moffatt Oxidation • Oxidation of Alcohols by DMSO • Preparation of Alcohols • Preparation of Alkylbenzene • Preparation of Amines • Reactions of Alcohols • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Dihalides • Reactions with Organometallic Reagents • Ritter Reaction • Sharpless Olefin Synthesis • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Swern Oxidation • Vilsmeier-Haack Reaction

Related Functional Groups of
[ 145691-59-4 ]

Aryls

A122781 [51760-22-6]

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Similarity: 0.97

A218176 [15852-73-0]

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A166505 [666747-06-4]

(2,4-Dibromophenyl)methanol

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A226129 [100751-63-1]

6-Bromo-2-naphthylmethanol

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A605696 [873-75-6]

(4-Bromophenyl)methanol

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Bromides

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(5-Bromo-1,3-phenylene)dimethanol

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(3-Bromophenyl)methanol

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A166505 [666747-06-4]

(2,4-Dibromophenyl)methanol

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A226129 [100751-63-1]

6-Bromo-2-naphthylmethanol

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A605696 [873-75-6]

(4-Bromophenyl)methanol

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Alcohols

A122781 [51760-22-6]

(5-Bromo-1,3-phenylene)dimethanol

Similarity: 0.97

A218176 [15852-73-0]

(3-Bromophenyl)methanol

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A166505 [666747-06-4]

(2,4-Dibromophenyl)methanol

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A226129 [100751-63-1]

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H420	Harms public health and the environment by destroying ozone in the upper atmosphere

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