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CAS No. : | 452-79-9 | MDL No. : | MFCD00143162 |
Formula : | C7H6FI | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | XVHYSMVSLDIUCM-UHFFFAOYSA-N |
M.W : | 236.03 | Pubchem ID : | 2774524 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 18-crown-6 ether; johnphos; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In tert-butyl alcohol; at 20℃; | Example 180 (5R)-7-(2-Fluoro-4-methylphenyl)-2-(trans-4-hydroxycyclohexyl)-2,7-diazaspiro[4.5]decan-l- one H A mixture of (5R)-2-(fralphar°-4-hydroxycyclohexyl)-2,7-diazaspiro[4.5]decan-l-one (20 mg, 0.00007 mol, this compound was prepared by using procedures analogous to those described in example 1, steps 1-5), 4-methyl-2-fluoro-l-iodobenzene (21 mg, 0.00009 mol), sodium tert-bvAoxide (9.98 mg, 0.000104 mol), 1,4,7,10,13,16-hexaoxacyclooctadecane (27.4 mg, 0.000104 mol) , 2-(di- tert-butylphosphino)biphenyl (0.8 mg, 0.000003 mol) , tris(diben2ylideneacetone)dipalladium(0) (1 mg, 0.000001 mol), in tert-butyl alcohol (1.0 mL, 0.010 mol) was stirred at rt for 18. The crude product was purified by prep-HPLC to afford the desired product. . LC-MS: 361.1 (MfH)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With potassium phosphate;copper(l) iodide; In ethylene glycol; butan-1-ol; at 100℃; | A mixture of (3S)-piperidin-3-ol hydrochloride (0.50 g, 0.0036 mol), 2-fluoro-l-iodo-4- methylbenzene (1.03 g, 0.00436 mol), copper(I) iodide (140 mg, 0.00073 mol), potassium phosphate (3.08 g, 0.0145 mol), and 1,2-ethanediol (0.810 mL, 0.0145 mol) in 1-butanol (7.28 mL, 0.0796 mol) <n="54"/>was heated at 100 0C under nitrogen for 2 nights. The reaction mixture was treated with water, and then extracted with EtOAc. The organic layers were combined, washed with brine, dried and evaporated to dryness. The residue was used directly in next step (519 mg, 69%). LCMS (M+H):210.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With N-Bromosuccinimide;dibenzoyl peroxide; In tetrachloromethane; for 20h;Heating / reflux; | A mixture of <strong>[452-79-9]3-fluoro-4-iodotoluene</strong> (2.26g, 9.58mmol), N-bromosuccinimide (2.03g, 11.49mmol) and benzoyl peroxide (5mol%, 116mg, 0.48mmol) in carbon tetrachloride (5ml) was stirred at reflux for 20 hours, cooled, diluted with dichloromethane and filtered. The purple coloured filtrate was washed with saturated sodium thiosulphate solution (aq) (20ml). The organic layer was separated, dried over sodium sulphate and the solvent removed by rotary evaporation to give the title compound as a yellow oil (2.58g, 86%).1 H-NMR (250MHz, CDCI3): 4.41 (2H, s), 6.94 (1 H, m), 7.11 (1 H, m), 7.72 (1 H, m). |
86% | With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 20h;Reflux; | A mixture of <strong>[452-79-9]3-fluoro-4-iodotoluene</strong> (2.26 g, 9.58 mmol), N-bromosuccinimide (2.03 g, 11.49 mmol) and benzoyl peroxide (5 mol %, 116 mg, 0.48 mmol) in carbon tetrachloride (5 ml) was stirred at reflux for 20 hours, cooled, diluted with dichloromethane and filtered. The purple coloured filtrate was washed with saturated sodium thiosulphate solution (aq) (20 ml). The organic layer was separated, dried over sodium sulphate and the solvent removed by rotary evaporation to give the title compound as a yellow oil (2.58 g, 86%).1H-NMR (250 MHz, CDCl3): delta 7.72 (1H, m), 7.11 (1H, m), 6.94 (1H, m), 4.41 (2H, s). |
86% | With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 20h;Reflux; | N-Bromosuccinimide (2.63g, 14.78mmol) and benzoylperoxide (0.20g, 0.62mmol) were added to a solution of <strong>[452-79-9]3-fluoro-4-iodotoluene</strong> (2.90g, 12.29mmol) in 7mL of tetrachloromethane. The resulting solution was refluxed for 20h. Thereafter, the reaction was allowed to cool to room temperature and was then diluted with 30mL of CH2Cl2. The solid phase was filtered off and the filtrate was washed with 30mL of a saturated solution of sodium thiosulphate. The organic layer was dried over Na2SO4 and evaporated. The crude product was purified by flash chromatography (AcOEt/PE 2:98), giving 3.45g (86%) of 8 as a white solid. Rf=0.76 (AcOEt/PE 5:95); mp=46-48C. 1H NMR (600MHz, CDCl3) delta 7.71 (m, 1H), 7.11 (m, 1H), 6.94 (m, 1H), 4.41 (s, 2H); 13C NMR (150MHz, CDCl3) delta 161.0 (J=246.5Hz), 140.6 (J=7.6Hz), 139.9 (J=1.3Hz), 126.4 (J=3.2Hz), 116.4 (J=24.5Hz), 81.3 (J=25.6Hz), 31.5; 19F (564MHz, CDCl3) delta -92.9 (t, J=7.3Hz). Anal. calcd for C7H5BrFI: C, 26.70; H, 1.60; found: C, 26.70; H, 1.58. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tert-butylate; tetrabutyl ammonium fluoride; bis[2-(diphenylphosphino)phenyl] ether;tris-(dibenzylideneacetone)dipalladium(0); In tetrahydrofuran; toluene; at 100℃; | Step 7: The product from the previous step was dissolved in dry toluene (8mL) under argon. A portion of this stock solution (ImL) was added to a reaction-vial in a Mettler-Toledo Bohdan block using an atmosphere of argon to exclude air. 2-Fluoro-l-iodo-4-methyl-benzene (0.33mmol; prepared from 2-fluoro-4-methyl-phenylamine according to a general literature procedure [S. E. Tunney and J. K. Stille, J. Org. Chem., 52, 748-53 (1987)]) was added as a toluene solution (ImL) followed by 0.5mL of a freshly prepared toluene stock of solution of <n="18"/>tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3) and bis[(2-diphenyl- phosphanyl)phenyl] ether DPEphos (corresponding to 0.3 equivalents palladium and 0.6 equivalents DPEphos). Potassium t°t-butoxide (0.66mmol) was added followed by tetra-n- butyl ammonium fluoride (TBAF; 1.0M in THF; 80 microliter). The mixture was stirred at 1000C overnight under argon. Next morning, the volatiles were removed using a Genevac instrument. The residue was dissolved in methanol (4mL) and loaded onto a VacMaster SCX- column (activated with 10% acetic acid in methanol). The product was eluted with acetonitrile. The volatiles were removed in vacuo. The residue was dissolved in methanol (1.5mL) and 4M HCl in diethyl ether (1.5mL) was added. The mixture was shaken at room temperature over the weekend before the volatiles were removed in vacuo. The residue was dissolved in dimethyl sulfoxide (0.18mL) and filtered. A few drops of 20% acetonitrile in water were added, and the mixture was filtered again. The product was isolated by preparative LC/MS as described, concentrated in vacuo, and the product was dissolved in dimethyl sulfoxide (0.78mL) to give a 1OmM solution. LC/MS-data: Method 14, retention time (UV) 2.152 min; UV-purity 79.5%; ELS-purity 100%; mass observed 337.407. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tert-butylate; bis[2-(diphenylphosphino)phenyl] ether;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 0℃; for 3h;Heating / reflux; | Step 7: The product from the previous step was added to an ice-cooled suspension of potassium tert-butoxide (95.4g) in toluene (2.8L) over ~2h. Then l-bromo-2-fiuoro-4-methyl- benzene (12Ig), tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3;1.7g) and bis(2-diphenyl- phosphanyl)ether (DPEphos; 2.48g) were added, and the mixture was refiuxed for ~lh. The crude mixture was cooled to room temperature and filtered through silica gel, and concentrated in vacuo to give the crude product (24Og). |
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