Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 21149-17-7 | MDL No. : | MFCD00056245 |
Formula : | C12H13NO4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | STFUIEDYPRMRNN-UHFFFAOYSA-N |
M.W : | 235.24 | Pubchem ID : | 3525700 |
Synonyms : |
|
Signal Word: | Warning | Class: | |
Precautionary Statements: | P264-P270-P301+P312+P330-P501 | UN#: | |
Hazard Statements: | H302 | 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 |
---|---|---|
94% | With sodium methylate In methanol at 0℃; for 0.5h; | |
84% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In chloroform at 60℃; for 1h; | |
60% | With quinoline; hydroquinone 1.) 120 deg C, 1 h, 2.) r.t., 20 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With potassium fluoride on basic alumina In tetrahydrofuran for 24h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With hydrazine hydrate In ethanol addition at 0 deg C; 30 min, room temperature, then 3 h, 90 deg C; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With triethylamine In tetrachloromethane for 18h; Ambient temperature; | |
Multi-step reaction with 2 steps 1: 38 percent / NaI / acetone / 4.5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With N,N-phenylbistrifluoromethane-sulfonimide; TEA In dichloromethane for 16h; Ambient temperature; | |
98% | With N,N-phenylbistrifluoromethane-sulfonimide; TEA In dichloromethane for 16h; Ambient temperature; dehydration of β-hydroxy-α-amino acid derivatives with phenyltriflimide; | |
95% | With triethylamine; 3-diphenyloxyphosphinyl-2-oxazolidinone In acetonitrile Ambient temperature; |
92% | With methanesulfonyl chloride; triethylamine In dichloromethane at -15 - 20℃; Inert atmosphere; | |
92% | With methanesulfonyl chloride; triethylamine In dichloromethane at -15 - 20℃; for 1.5h; | Methyl 2-(benzyloxycarbonyl)acrylate To a flame dried three-neck round bottom flask, fitted with a mechanical stirrer, was added (S)-methyl 2-(benzyloxycarbonyl)-3- hydroxypropanoate (129 g, 509 mmoles), anhydrous dichloromethane (2 L), and methanesulfonyl chloride (49.3 mL, 636 mmoles). The mixture was cooled to -15°C, and treated with triethylamine (213 mL, 1527 mmoles), dropwise, to ensure the temperature of the reaction mixture did not exceed 0°C. The addition of the first equivalent of triethylamine was exothermic. After addition of triethylamine, the mixture was stirred at 0°C for 30 min. The cooling bath was removed and the mixture stirred at room temperature for 1.5 h. The reaction was quenched by addition of methanol (21 mL). The mixture was washed with 0.5% aqueous potassium bisulfate until the washings were pH 5, then saturated sodium bicarbonate, and brine, dried over sodium sulfate, and concentrated. Flash chromatography (silica gel, 1:9 ethyl acetate/hexanes) gave 111 g (92%) as a viscous colorless oil, which crystallized upon standing. 1H-NMR (DMSO-d6) d 3.71 (s, 3 H), 5.10 (s, 2 H), 5.60 (s, 1 H), 5.76 (s,1, H), 7.39-7.35 (m, 5 H), 8.96 (s, 1 H); 13C-NMR (DMSO-d6) d 52.3, 65.9, 127.8, 128.1, 128.3, 128.8, 133.3, 136.3, 153.5, 163.7. |
90% | With di(succinimido) carbonate; triethylamine In acetonitrile for 4h; Ambient temperature; | |
90% | With tris-(2-chloro-ethyl)-amine; triphenylphosphine; diethylazodicarboxylate In toluene at 0℃; for 3h; | |
89% | With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; copper(l) chloride In chloroform for 5h; Ambient temperature; | |
85% | With triethylamine; 1,1'-carbonyldiimidazole In tetrahydrofuran for 6h; Ambient temperature; | |
With N,N-dimethylformamide dineopentyl acetal In benzene Heating; | ||
With copper(l) chloride; diisopropyl-carbodiimide In dichloromethane | ||
With triethylamine; propynoic acid benzylamide In chloroform for 24h; | ||
Multi-step reaction with 2 steps 1: Et3N 2: NaN3 / dimethylformamide / 4 h / 40 °C | ||
Multi-step reaction with 2 steps 1: 64 percent / Ph3P, CCl4 / 24 h / Heating 2: 98 percent / Et3N / CCl4 / 18 h / Ambient temperature | ||
Multi-step reaction with 3 steps 1: 64 percent / Ph3P, CCl4 / 24 h / Heating 2: 38 percent / NaI / acetone / 4.5 h / Heating | ||
137 kg | Stage #1: N-benzyloxycarbonyl-L-serine methyl ester With methanesulfonyl chloride In tetrahydrofuran at 0 - 25℃; for 1h; Large scale; Stage #2: With triethylamine In tetrahydrofuran at 25℃; for 2h; Large scale; | |
Multi-step reaction with 2 steps 1: dmap / acetonitrile / 20 °C 2: N,N,N',N'-tetramethylguanidine / acetonitrile / 20 °C | ||
Multi-step reaction with 2 steps 1: dmap / acetonitrile / 8 h / 22 °C / Inert atmosphere 2: N,N,N',N'-tetramethylguanidine / acetonitrile / 8 h / 22 °C / Inert atmosphere; Darkness |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With silver carbonate In methanol; water for 8.5h; Heating; | |
With triethylamine; N1-benzyl-2-heptynamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With diisopropyl-carbodiimide In acetonitrile at 40℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 73% 2: 13% | With triphenylphosphine; diethylazodicarboxylate In benzene for 15h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 53% 2: 28% | With triphenylphosphine; diethylazodicarboxylate In benzene for 15h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 12% 2: 12% | In tetrahydrofuran for 15h; Heating; | |
1: 12% 2: 12% | In tetrahydrofuran for 15h; Heating; Yield given. Title compound not separated from byproducts; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tetrabutyl ammonium fluoride In toluene for 22h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium fluoride; 18-crown-6 ether In toluene for 5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 35% 2: 22% | With tetrabutyl ammonium fluoride In dichloromethane for 4h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | In methanol at 45 - 50℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With copper(l) iodide; zinc In tetrahydrofuran; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With dmap; 1,8-diazabicyclo[5.4.0]undec-7-ene; p-toluenesulfonyl chloride; In acetonitrile; at 20℃;Molecular sieve; | General procedure: 4-Toluenesulfonic chloride (TsCl) (2.0 eq) and 4-dimethylaminopyridine (DMAP) (0.2 eq) were added subsequently to the solution of N-Boc-DL-Ser-O-Me (1.0 eq) in acetonitrile (0.2 M, containing MS (4A) (40 mg/mmol)) at r.t., 1,8-diazobicyclo[5,4,0]undec-7-ene (DBU) (5.0 eq) was added dropwisely to the solution, whose color darkened during the addition, the reaction was monitored by thin layer chromatography (TLC). When starting material was consumed, the mixture was diluted with ethyl acetate, washed with saturated citric acid, followed by water, then by brine. The organic phase was dried over anhydrous sodium sulfate. Crude product was obtained after concentration, which was purified through flash chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With copper(l) iodide; zinc In tetrahydrofuran; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 69% 2: 17% | With triethyl borane; tri-n-butyl-tin hydride In hexane; toluene at 20℃; Irradiation; sonication; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With manganese; diphenylphosphane In tetrahydrofuran for 6h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With triethylamine; tris-(o-tolyl)phosphine; palladium dichloride In acetonitrile at 90℃; for 4h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; triethylamine In N,N-dimethyl-formamide at 100℃; for 9h; | |
86% | With triethylamine In N,N-dimethyl-formamide at 100℃; for 9h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With bis(1,5-cyclooctadiene)rhodium(I) hexafluorophosphate; 1,3-bis-(diphenylphosphino)propane In water; toluene at 110 - 115℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium azide In N,N-dimethyl-formamide at 40℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With triethylamine; lithium chloride In N,N-dimethyl-formamide at 90℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With tetrabutyl-ammonium chloride; triethylamine In tetrahydrofuran at 70℃; for 2.5h; | |
74% | With tetrabutyl-ammonium chloride; palladium diacetate; triethylamine In tetrahydrofuran at 70℃; for 4.5h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 57% 2: 16% | With tetrabutyl-ammonium chloride; triethylamine In tetrahydrofuran at 70℃; for 2.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With tetrabutyl-ammonium chloride; triethylamine In tetrahydrofuran at 70℃; for 2.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With tetrabutyl-ammonium chloride; triethylamine In tetrahydrofuran at 70℃; for 2.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium carbonate In N,N-dimethyl-formamide at 65℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 74 percent / tetrabutylammonium chloride; Et3N / palladium(II) acetate / tetrahydrofuran / 2.5 h / 70 °C 2: 95 percent / hydrogen; (+)-1,2-bis((2S,5S)-2,5-Et2phospholano)Ph(c-octadiene)Rh*BF4 / CH2Cl2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 74 percent / tetrabutylammonium chloride; Et3N / palladium(II) acetate / tetrahydrofuran / 2.5 h / 70 °C 2: 95 percent / hydrogen; (+)-1,2-bis((2S,5S)-2,5-Et2phospholano)Ph(c-octadiene)Rh*BF4 / CH2Cl2 3: 99 percent / magnesium methoxide / CHCl3; methanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 74 percent / tetrabutylammonium chloride; Et3N / palladium(II) acetate / tetrahydrofuran / 2.5 h / 70 °C 2: 95 percent / hydrogen; (+)-1,2-bis((2S,5S)-2,5-Et2phospholano)Ph(c-octadiene)Rh*BF4 / CH2Cl2 3: 99 percent / magnesium methoxide / CHCl3; methanol 4: 86 percent / thionyl chloride / CH2Cl2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 74 percent / tetrabutylammonium chloride; Et3N / palladium(II) acetate / tetrahydrofuran / 2.5 h / 70 °C 2: 95 percent / hydrogen; (+)-1,2-bis((2R,5R)-2,5-Et2phospholano)Ph(c-octadiene)Rh*BF4 / CH2Cl2; methanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 74 percent / tetrabutylammonium chloride; Et3N / palladium(II) acetate / tetrahydrofuran / 2.5 h / 70 °C 2: 95 percent / hydrogen; (+)-1,2-bis((2R,5R)-2,5-Et2phospholano)Ph(c-octadiene)Rh*BF4 / CH2Cl2; methanol 3: 99 percent / magnesium methoxide / CHCl3; methanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 75 percent / Et3N / 72 h / 20 °C 2: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 3: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 4: 85 percent / trifluoroacetic acid / 1 h / 20 °C | ||
Multi-step reaction with 5 steps 1: 75 percent / Et3N / 72 h / 20 °C 2: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 3: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 4: Et3N, MnO2 / CH2Cl2 5: 85 percent / trifluoroacetic acid / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 75 percent / Et3N / 72 h / 20 °C 2: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 75 percent / Et3N / 72 h / 20 °C 2: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 3: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min | ||
Multi-step reaction with 4 steps 1: 75 percent / Et3N / 72 h / 20 °C 2: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 3: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 4: Et3N, MnO2 / CH2Cl2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 75 percent / Et3N / 72 h / 20 °C 2: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 3: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 60 percent / Ph3P, dimethyl azodicarboxylate / tetrahydrofuran / 2.5 h / 20 °C 2: 12 percent / methanol; tetrahydrofuran / 0.42 h / 22 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 97 percent / conc. hydrochloric acid, zinc / methanol / 0.25 h / 0 °C 2: 92 percent / Fetizon's reagent / methanol; H2O / 8.5 h / Heating | ||
Multi-step reaction with 4 steps 1: Acetic anhydride, Cl2 / CH2Cl2 / 1.) 0 deg C; 2.) room temp., 1 h 2: 35 percent / CH2Cl2; diethyl ether / undried Diazomethane solution; 1.) 0 deg C; 2.) room temp., 1 h 3: LiBH4 / 1,2-dimethoxy-ethane / 1.) -78 deg C; 2.) room temp., 2 h 4: Sodium methyl mercaptide, Tetraethylammonium chloride / H2O; CHCl3 / 4 h / Ambient temperature | ||
Multi-step reaction with 4 steps 1: Acetic anhydride, Cl2 / CH2Cl2 / 1.) 0 deg C; 2.) room temp., 1 h 2: 80 percent / CH2Cl2; diethyl ether / CH2N2 dried over KOH pellets 3: LiBH4 / 1,2-dimethoxy-ethane / 1.) -78 deg C; 2.) room temp., 2 h 4: Sodium methyl mercaptide, Tetraethylammonium chloride / H2O; CHCl3 / 4 h / Ambient temperature |
Multi-step reaction with 3 steps 1: Acetic anhydride, Cl2 / CH2Cl2 / 1.) 0 deg C; 2.) room temp., 1 h 2: 82 percent / LiBr / tetrahydrofuran; diethyl ether; CH2Cl2 / 0 °C 3: Sodium methyl mercaptide, Tetraethylammonium chloride / H2O; CHCl3 / 4 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: d,l-2-methoxy-α-methylbenzyl bromide; methyl 2-(benzyloxycarbonylamino)acrylate With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene at 80℃; for 5h; Stage #2: With potassium hydroxide In methanol; water at 20℃; Stage #3: With hydrogenchloride In water | A Example A; Synthesis of 2(RS)-benzyloxycarbonylamino-4(RS)-(2-methoxyphenyl)pentanoic acid To d,l-2-methoxy-α-methylbenzyl alcohol (0.5 g, 3.29 mmol) was added 48% aq. HBr (2 mL) and the reaction mixture was stirred rapidly for 1.5 h. The reaction mixture was diluted with hexane (30 mL), washed with water, dried with MgSO4 filtered, and evaporated under vacuum. The crude d,l-2-methoxy-α-methylbenzyl bromide was added to a solution of tributyltin hydride (0.67 mL, 2.49 mmol), Z-dehydroalanine methyl ester (0.25 g, 1.06 mmol), and 2,2'-azobisisobutyronitrile (15 mg, 0.09 mmol) in benzene (5 mL). The reaction mixture was heated at 80 °C under a nitrogen atmosphere for 5 h. Benzene was removed under vacuum and the residue was dissolved in methanol (20 mL). 2N KOH (5 mL) was added and the mixture was rapidly stirred at room temperature over night. Methanol was removed under vacuum and the residue was diluted with water (20 mL). The aqueous solution was washed with ether to remove the tin by- products. The aqueous layer was acidified with 6 N HCl (aq.) and the product was extracted with ethyl acetate. The combined organic layers were washed with brine, dried with MgSO4, filtered, and evaporated under vacuum to give 2-benzyloxy-carbonylamino-4-(2-methoxyphenyl)pentanoic acid (190 mg, 0.53 mmol) as a mixture ofdiastereomers in sufficiently pure form to be used without further purification. MS: (M++H) 358, (M+-H) 356. | |
Stage #1: d,l-2-methoxy-α-methylbenzyl bromide; methyl 2-(benzyloxycarbonylamino)acrylate With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene at 80℃; for 5h; Stage #2: With methanol; potassium hydroxide; water at 20℃; Stage #3: With hydrogenchloride In water | A Example A; Atty. Docket No. CLOOl 532 PCT 54 EPO Synthesis of 2(i^-benzyloxyearbonylamino-4(i^-(2-methoxyphenyl)pentanoic acid To d,/-2-methoxy-α-methylbenzyl alcohol (0.5 g, 3.29 mmol) was added 48% aq. HBr(2 niL) and the reaction mixture was stirred rapidly for 1.5 h. The reaction mixture was diluted with hexane (30 mL), washed with water, dried with MgSO41 filtered, and evaporated under vacuum. The crude d,l-2-methoxy-α-methylbenzyl bromide was added to a solution of tributyltin hydride (0.67 mL, 2.49 mmol), Z-dehydroalanine methyl ester (0.25 g, 1.06 mmol), and 2,2'-azobisisobutyronitrile (15 mg, 0.09 mmol) in benzene (5 mL). The reaction mixture was heated at 80 0C under a nitrogen atmosphere for 5 h. Benzene was removed under vacuum and the residue was dissolved in methanol (20 mL). 2N KOH (5 mL) was added and the mixture was rapidly stirred at room temperature over night. Methanol was removed under vacuum and the residue was diluted with water (20 mL). The aqueous solution was washed with ether to remove the tin by products. The aqueous layer was acidified with 6 N HCl (aq.) and the product was extracted with ethyl acetate. The combined organic layers were washed with brine, dried with MgSO4, filtered, and evaporated under vacuum to give 2-benzyloxy- carbonylamino-4-(2-methoxyphenyl)pentanoic acid (190 mg, 0.53 mmol) as a mixture of diastereomers in sufficiently pure form to be used without further purification. MS: (M4M-H) 358, (M+-H) 356. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene for 2h; Heating / reflux; | G.2 Step 2; Tributyltin hydride (37.8 g, 130 mmol) was added at reflux to a 500 ml of flask charged with benzene (200 ml) was added Z-dehydro-Ala methyl ester (15 g, 64 mmol), 1-methylcyclopentyl bromide (20.5 g) and AIBN (1.9 g). After 2 h, the solvent was removed and the residue was purified by column chromatograph to yield 2-benzyloxycarbonylamino-3-(l - methylcyclopentyl)propionic acid methyl ester (7.9 g). | |
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene for 2h; Heating / reflux; | L.2 Tributyltin hydride (37.8 g, 130 mmol) was added at reflux to a 500 ml of flask charged with benzene (200 mL) was added Z-dehydro-Ala-OH (15 g, 64 mmol), 1-methylcyclopentanyl- bromide (20. 5 g) and AIBN (1.9g). After 2 h, the solvent was removed and the residue was purified by column chromatograph to yield 7.9g of 2-benzyloxyzarbonylamino-3-(l-methyl- cyclopentyl) propionic acid methyl ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Z) -Methyl 3- (4-amino-3, 5-dimethylphenyl)-2- (benzyloxycarbonyl) acrylate; A 2 L round bottom flask, was charged with 4-iodo-2,6- dimethylbenzenamine hydrochloride salt (55 g, 194 mmol), methyl 2- (benzyloxycarbonyl) acrylate (59.2 g, 252 mmol), tetrabutylammonium chloride (59.2 g, 213 mmol), palladium acetate (4.34 g, 19.4 mmol), and tetrahydrofuran (1.2 L, degassed by a flow of nitrogen for 30 min). The mixture was stirred to form a suspension and degassed by a flow of nitrogen for 30 min. Triethylamine (110 mL, 789 mmol) was then added and the resulting mixture was heated at reflux for 3h. After cooling to room temperature, the reaction mixture was filtered through a pad of celite and washed twice with tetrahydrofuran (2 x 100 mL). The solvents were removed and the residue was dissolved in methylene chloride which was extracted with water (3X), brine (2X), dried over sodium sulfate and concentrated. Column chromatography on silica gel using 1: 9 ethyl acetate/methylene chloride as eluent afforded a tan solid, which was recrystalized from methanol (210 mL) and water (100 mL). After filtration, the solid was washed with ice cold 1: 1 methanol/water mixture and then dried under high vacuum overnight at room temperature to afford the title compound (58.0 g, 65%) as a light tan solid. NMR shows a 2.7 : 1 ratio of Z and E isomers which were not separated.'H-NMR (DMSO-d6) 8 8.79 (s, 0.73H), 8.51 (s, 0.27 H), 7.40-7. 21 (m, 8H), 5.24 (s, 2H), 5.13 (s, 1.46 H), 5.00 (s, 0.54 H), 3.68 (s, 2.2 H), 3.61 (s, 0.8 H), 2.05 (s, 6H) ;'3C-NMR (DMSO-d6) 8166. 0,154. 7,146. 9, 137.2, 135.8, 130.9, 128.3, 127. 7, 127. 3,120. 3,120. 0,119. 4,65. 3,51. 7,17. 8. | ||
A 2 L round bottom flask was charged <strong>[138385-59-8]4-iodo-2,6-dimethylbenzenamine hydrochloride</strong> salt (55 g, 194 mmol), methyl 2-(benzyloxycarbonyl)acrylate (59.2 g, 252 mmol), tetrabutylammonium chloride (59.2 g, 213 mmol), palladium (II) acetate (4.34 g, 19.4 mmol), and tetrahydrofuran (1.2 L, degassed by a flow of nitrogen for 30 min). The mixture was stirred so that a suspension was formed and then degassed by a flow of nitrogen for 30 min. Triethylamine (10 mL, 789 mmol) was added and the resulting mixture was heated at reflux for 3 h. After cooling to room temperature, the reaction mixture was filtered through a pad of celite, washed with tetrahydrofuran (2×100 mL), and concentrated. The residue was dissolved in dichloromethane, washed with water (3×) and brine (2×), dried over sodium sulfate, and concentrated. Flash chromatography (silica gel using 1:9 ethyl acetate/dichloromethane) gave a tan solid. The solid was recrystallized from warm methanol (210 mL) and water (100 mL). The mixture was held at room temperature overnight, then at 0 C. for 2 h, and finally at -15 C. for 2 h. The resulting solid was filtered, washed with ice cold 1:1 methanol/water, and dried under high vacuum overnight to give 44.7 g (65%) as a light tan solid which was a mixture of Z/E isomers (73:27). 1H-NMR (DMSO-d6) 6, 2.05 (s, 6H), 3.61 (s, 0.8H), 3.68 (s, 2.2H), 5.00 (s, 0.54H), 5.13 (s, 1.46H), 5.24 (s, 2H), 7.40-7.21 (m, 8H), 8.51 (s, 0.27H), 8.79 (s, 0.73H); 13C-NMR (DMSO-d6) delta 17.8, 51.7, 65.3, 119.4, 120.0, 120.3, 127.3, 127.7, 128.3, 130.9, 135.8, 137.2, 146.9, 154.7, 166.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine at 0 - 20℃; for 2h; | Methyl 2- (benzyloxycarbonyl) acrylate U CbzNH C02Me; To a flame dried three neck round bottom flask, was added methyl 2- (benzyloxycarbonyl) -3-hydroxypropanoate (129 g, 509 mmol), anhydrous methylene chloride (2 L), and methanesulfonyl chloride (49.3 mL, 636 mmol). The mixture was cooled to-15°C ~ 20°C for 20 min while stirring with a mechanical stirrer. Triethylamine (213 mL, 1527 mmol) was added dropwise ensuring the inner temperature of the reaction mixture did not exceed 0°C (the addition of the first equivalent of triethylamine was exothermic). After the addition of triethylamine, the mixture was stirred at 0°C for 30 min, then the cooling bath was removed and the mixture was stirred at room temperature for 1.5 h. Methanol (21 mL) was added to quench excess methanesulfonyl chloride. The mixture was washed portionwise with 0.5% aq. potassium hydrogen sulfate to pH 5, then sat. sodium bicarbonate/brine (1: 2 by volume) and brine. The methylene chloride solution was dried over anhydrous sodium sulfate. After filtration, the solvents were removed and the residue was subjected to column chromatography on silica gel using 1: 9 ethyl acetate/hexanes as eluent to afford the title compound as a colorless very viscous oil, which recrystalized upon standing at room temperature, 0°C and-15°C (111 g, 92% yield).'H-NMR (DMSO-d6) 8 8.96 (s, 1H), 7.39-7. 35 (m, 5H), 5.76 (s, 1H), 5.60 (s, 1H), 5.10 (s, 2H), 3.71 (s, 3H) ;'C-NMR (DMSO) § 163.7, 153.5, 136.3, 133.3, 128.8, 128.3, 128.1, 127.8, 65.9, 52.3. | |
With triethylamine In tetrahydrofuran at 0 - 20℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene at 80℃; for 5h; | B To d, l-2-methoxy-a-methylbenzyl alcohol (0.5 g, 3.29 mmol) was added 48% aq. HBr (2 mL) and the reaction mixture was stirred rapidly for 1.5 h. The reaction mixture was diluted with hexane (30 mL), washed with water, dried with MgS04, filtered, and evaporated under vacuum. The crude d, 1-2-methoxy-a-methylbenzyl bromide was added to a solution of tributyltin hydride (0.67 mL, 2.49 mmol), Z-dehydroalanine methyl ester (0.25 g, 1.06 mmol), and 2, 2'-azobisisobutyronitrile (15 mg, 0.09 mmol) in benzene (5 mL). The reaction mixture was heated at 80 °C under a nitrogen atmosphere for 5 h. Benzene was removed under vacuum and the residue was dissolved in methanol (20 mL). 2N KOH (5 mL) was added and the mixture was rapidly stirred at room temperature over night. Methanol was removed under vacuum and the residue was diluted with water (20 mL). The aqueous solution was washed with ether to remove the tin by products. The aqueous layer was acidified with 6 N HC1 (aq. ) and the product was extracted with ethyl acetate. The combined organic layers were washed with brine, dried with MgS04, filtered, and evaporated under vacuum to give 2-benzyloxy-carbonylamino-4- (2- methoxyphenyl) pentanoic acid (190 mg, 0.53 mmol) as a mixture of diastereomers in sufficiently pure form to be used without further purification. MS: (M++H) 358, (M+-H) 356. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-(2-methoxyphenyl)ethanol With hydrogen bromide In water for 1.5h; Stage #2: methyl 2-(benzyloxycarbonylamino)acrylate With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene at 80℃; for 5h; Stage #3: With hydrogenchloride; potassium hydroxide more than 3 stages; | A Example A; Synthesis of 2(i?5)-benzyloxycarbonylaniino-4(i?S)-(2-methoxyphenyl)pentanoic acid; To d,/-2-methoxy-α-methylbenzyl alcohol (0.5 g, 3.29 mmol) was added 48% aq. HBr (2 ml) and the reaction mixture was stirred rapidly for 1.5 h. The reaction mixture was diluted with hexane (30 ml), washed with water, dried with MgSO4j filtered, and evaporated under vacuum. The crude d,l-2-methoxy-α-methylbenzyl bromide was added to a solution of tributyltin hydride (0.67 ml, 2.49 mmol), Z-dehydroalanine methyl ester (0.25 g, 1.06 mmol), and 2,2'-azobisisobutyronitrile (15 mg, 0.09 mmol) in benzene (5 ml). The reaction mixture was heated at 80 0C under a nitrogen atmosphere for 5 h. Benzene was removed under vacuum and the residue was dissolved in methanol (20 ml). 2N KOH (5 ml) was added and the mixture was rapidly stirred at room temperature over night. Methanol was removed under vacuum and the residue was diluted with water (20 ml). The aqueous solution was washed with ether to remove the tin by products. The aqueous layer was acidified with 6 N HCl (aq.) and the product was extracted with ethyl acetate. The combined organic layers were washed with brine, dried with MgSO4, filtered, and evaporated under vacuum to give 2-benzyloxy-carbonylamino-4-(2-methoxyphenyl)pentanoic acid (190 mg, 0.53 mmol) as a mixture of diastereomers in sufficiently pure form to be used without further purification. MS: (M++H) 358, (M+-H) 356. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tetrabutyl-ammonium chloride; palladium diacetate; triethylamine In tetrahydrofuran at 70℃; for 4.5h; stereoselective reaction; | |
69% | With tetrabutyl-ammonium chloride; sodium hydrogencarbonate In tetrahydrofuran for 3.75h; Heating / reflux; | 3-(2-Acetoxymethyl-4-tert-butoxycarbonylamino-3-methyl-phenyl)-2-benzyloxycarbonylamino-acrylic acid methyl ester. Palladium (II) acetate (105 mg, 0.43 mmol) was added to a mixture of acetic acid 3-tert-butoxycarbonylamino-6-iodo-2-methyl-benzyl ester (2.89 g, 7.1 mmol), Z-dehydroalanine methyl ester (2.20 g, 9.4 mmol), tetrabutylammonium chloride hydrate (2.70 g, 9.7 mmol), and sodium bicarbonate (1.80 g, 21.4 mmol) in THF (100 mL). Reaction was heated at reflux for 3.75 hours. Mixture was cooled to room temperature then filtered through a plug of silica gel eluting 70% ethyl acetate-hexanes (500 mL). Filtrate was concentrated in vacuo. Silica gel chromatography afforded the title compound as a yellow solid in 69% yield. 1H NMR (300 MHz, CDCl3): δ=7.79 (d, J=8.4, 1H), 7.42 (s, 1H), 7.27 (m, 6H), 6.30 (s, 1H), 5.11 (s, 2H), 5.02 (s, 2H), 3.81 (s, 3H), 2.21 (s, 3H), 2.02 (s, 3H), 1.51 (s, 9H). MS m/e (M-H)-=511.0. |
69% | With tetrabutyl-ammonium chloride; sodium hydrogencarbonate In tetrahydrofuran for 3.75h; Heating / reflux; | 3-(2-Acetoxymethyl-4-tert-butoxycarbonylamino-3-methyl-phenyl)-2-benzyloxycarbonylamino-acrylic acid methyl ester; Palladium (II) acetate (105 mg, 0.43 mmol) was added to a mixture of acetic acid 3-tert-butoxycarbonylamino-6-iodo-2-methyl-benzyl ester (2.89 g, 7.1 mmol), Z-dehydroalanine methyl ester (2.20 g, 9.4 mmol), tetrabutylammonium chloride hydrate (2.70 g, 9.7 mmol), and sodium bicarbonate (1.80 g, 21.4 mmol) in THF (100 mL). Reaction was heated at reflux for 3.75 hours. Mixture was cooled to room temperature then filtered through a plug of silica gel eluting 70% ethyl acetate-hexanes (500 mL). Filtrate was concentrated in vacuo. Silica gel chromatography afforded the title compound as a yellow solid in 69% yield. 1H NMR (300 MHz, CDCl3): δ=7.79 (d, J=8.4, 1H), 7.42 (s, 1H), 7.27 (m, 6H), 6.30 (s, 1H), 5.11 (s, 2H), 5.02 (s, 2H), 3.81 (s, 3H), 2.21 (s, 3H), 2.02 (s, 3H), 1.51 (s, 9H). MS m/e (M-H)-=511.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: (S)-methyl 2-(benzyloxycarbonyl)-3-hydroxypropanoate; methanesulfonyl chloride With triethylamine In dichloromethane at -15 - 0℃; for 0.5h; Stage #2: With methanol In dichloromethane at 20℃; for 1.5h; | To a flame dried three-neck round bottom flask, fitted with a mechanical stirrer, was added (S)-methyl 2-(benzyloxycarbonyl)-3-hydroxypropanoate (129 g, 509 mmol), anhydrous dichloromethane (2 L), and methanesulfonyl chloride (49.3 mL, 636 mmol). The mixture was cooled to -15° C., and treated with triethylamine (213 mL, 1527 mmol), dropwise, to ensure the temperature of the reaction mixture did not exceed 0° C. (The addition of the first equivalent of triethylamine was exothermic.) After addition of triethylamine, the mixture was stirred at 0° C. for 30 min. The cooling bath was removed and the mixture stirred at room temperature for 1.5 h. The reaction was quenched by addition of methanol (21 mL). The mixture was washed with 0.5% aqueous potassium bisulfate until the washings were pH 5, then saturated sodium bicarbonate, and brine, dried over sodium sulfate, and concentrated. Flash chromatography (silica gel, 1:9 ethyl acetate/hexanes) gave 111 g (92%) as a viscous colorless oil, which crystallized upon standing. 1H-NMR (DMSO-d6) δ 3.71 (s, 3H), 5.10 (s, 2H), 5.60 (s, 1H), 5.76 (s, 1H), 7.39-7.35 (m, 5H), 8.96 (s, 1H); 13C-NMR (DMSO-d6) δ 52.3, 65.9, 127.8, 128.1, 128.3, 128.8, 133.3, 136.3, 153.5, 163.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid In methanol | 7 EXAMPLE 7 EXAMPLE 7 In a nitrogen atmosphere, a solution prepared by admixing 65 mg of concentrated sulfuric acid with 10 ml of methanol was added to 20.08 g of N-benzyloxycarbonyl-S-phenyl-L-cysteine and 40 ml of methanol, and the reaction was allowed to proceed under reflux. After 50 hours of reaction, the mixture was cooled to about 25° C. The pH of the solution was 1.2. Then, the solution was cooled to -15° C. over 3 hours with vigorous stirring, and the resulting crystalline precipitate was filtered off and dried under reduced pressure to give 19.22 g (yield: 91%) of white crystals. The purity of these crystals of N-benzyloxycarbonyl-S-phenyl-L-cysteine methyl ester was 99.1% by weight and the optical purity was 99.9%. The formation of N-benzyloxycarbonyldehydroalanine methyl ester was not detected. | |
With sodium bicarbonate; p-toluenesulfonic acid monohydrate In methanol; water | 8 EXAMPLE 8 EXAMPLE 8 In a nitrogen atmosphere, 150 ml of methanol was added to 30.09 g of N-benzyloxycarbonyl-S-phenyl-L-cysteine and 864 mg of p-toluenesulfonic acid monohydrate, and the reaction was allowed to proceed under reflux. After 6 hours of reaction, the mixture was cooled to about 50° C. and adjusted to pH 8.0 by adding 10 ml of a 5% (by weight) aqueous solution of sodium hydrogen carbonate. Then, 110 ml of pure water was added dropwise over 3 hours with vigorous stirring at about 50° C., the resulting mixture was cooled to 5° C., and the resulting precipitate crystals were filtered off and washed in sequence with a mixed solution composed of 50 ml of methanol and 50 ml of pure water and with 100 ml of pure water and then dried under reduced pressure to give 30.89 g (yield: 98%) of white crystals. With these crystals, the purity of N-benzyloxycarbonyl-S-phenyl-L-cysteine methyl ester was 99.7% by weight and the optical purity was 99.8%. The formation of N-benzyloxycarbonyldehydroalanine methyl ester was not detected. The thus-obtained N-benzyloxycarbonyl-S-phenyl-L-cysteine methyl ester gave the following 400 MHz nuclear magnetic resonance spectrum (CDCl3; internal standard: TMS) δ: 3.36-3.45 (2H, m), 3.53 (3H,), 4.61-4.65 (1H, m), 5.03-5.10 (2H, ABq, J=12.5 Hz), 5.60-5.62 (1H, b), 7.17-7.45 (10H, m). | |
With sodium bicarbonate; sulfuric acid In methanol; water | 9 EXAMPLE 9 EXAMPLE 9 In a nitrogen atmosphere, a solution prepared by admixing 458 ml of concentrated sulfuric acid with 10 ml of methanol was added to 30.03 g of N-benzyloxycarbonyl-S-phenyl-L-cysteine and 140 ml of methanol, and the reaction was allowed to proceed under reflux. After 6 hours of reaction, the mixture was cooled to about 50° C. and adjusted to pH 8.0 by adding 15 ml of a 5% (by weight) aqueous solution of sodium hydrogen carbonate. Then, 105 ml of pure water was added dropwise over 3 hours with vigorous stirring at about 50° C., the resulting mixture was cooled to 5° C., and the precipitate crystals were then filtered off, washed in sequence with a mixed solution composed of 50 ml of methanol and 50 ml of pure water and with 100 ml of pure water, and dried under reduced pressure to give 30.67 g (yield: 98%) of white crystals, With these crystals, the purity of N-benzyloxycarbonyl-S-phenyl-L-cysteine methyl ester was 99.6% by weight and the optical purity was 99.8%. The formation of N-benzyloxycarbonyldehydroalanine methyl ester was not detected. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | Stage #1: methyl 2-(benzyloxycarbonylamino)acrylate With chlorine In dichloromethane at 0℃; for 0.0333333h; Stage #2: With 1,4-diaza-bicyclo[2.2.2]octane; air In acetonitrile at 0℃; for 0.25h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With N,N,N',N'-tetramethylguanidine In acetonitrile | |
52% | With N,N,N',N'-tetramethylguanidine In acetonitrile at 20℃; | |
6.03 g | With N,N,N',N'-tetramethylguanidine In acetonitrile at 22℃; for 8h; Inert atmosphere; Darkness; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: di-<i>tert</i>-butyl dicarbonate; N-benzyloxycarbonyl-L-serine methyl ester With dmap In acetonitrile at 20℃; Stage #2: With N,N,N',N'-tetramethylguanidine In acetonitrile Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: methyl 2-(benzyloxycarbonylamino)acrylate With N-Bromosuccinimide In dichloromethane for 16h; Stage #2: With triethylamine In dichloromethane for 1h; Further stages.; | |
Stage #1: methyl 2-(benzyloxycarbonylamino)acrylate With N-Bromosuccinimide In dichloromethane for 16h; Stage #2: With triethylamine In dichloromethane for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With bis(tri-tert-butylphosphine)palladium(0); N-Methyldicyclohexylamine; bis(dibenzylideneacetone)-palladium(0) In 1,4-dioxane at 20℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With bis(tri-tert-butylphosphine)palladium(0); N-Methyldicyclohexylamine; bis(dibenzylideneacetone)-palladium(0) In 1,4-dioxane at 20℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With indium In methanol at 50℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With tetrabutyl-ammonium chloride; palladium diacetate; triethylamine In tetrahydrofuran at 70℃; for 4.5h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With bis(tri-tert-butylphosphine)palladium(0); N-Methyldicyclohexylamine In 1,4-dioxane at 100℃; for 12h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With tetrabutyl-ammonium chloride; palladium diacetate; triethylamine In tetrahydrofuran at 70℃; for 4.5h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With bis(tri-tert-butylphosphine)palladium(0); N-Methyldicyclohexylamine In 1,4-dioxane at 100℃; for 12h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With bis(tri-tert-butylphosphine)palladium(0); N-Methyldicyclohexylamine In 1,4-dioxane at 100℃; for 12h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With bis(tri-tert-butylphosphine)palladium(0); N-Methyldicyclohexylamine In 1,4-dioxane at 100℃; for 12h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With tetrabutyl-ammonium chloride; palladium diacetate; sodium hydrogencarbonate In tetrahydrofuran at 70℃; for 6h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tetrabutyl ammonium fluoride In tetrahydrofuran at 28℃; for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With BF4(1-)*C49H54O4P2Rh(1+); hydrogen In tetrahydrofuran at 20℃; for 18h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
98% ee | With bis(norbornadiene)rhodium(l)tetrafluoroborate; C60H46O4P2; hydrogen In tetrahydrofuran at 20℃; for 18h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With potassium <i>tert</i>-butylate In dichloromethane at 20℃; for 0.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With tris-(dibenzylideneacetone)dipalladium(0); triethylamine; lithium chloride; johnphos In N,N-dimethyl-formamide at 80℃; Inert atmosphere; | 4 Step 4: Synthesis of R42 Step 4: Synthesis of R42 2-benzyloxycarbonylamino-acrylicacidmethylester (2.274g, 9.67 mmol), bis(dibenzylideneacetone) palladium (0) (295 mg, 0.32 mmol), (2-biphenylyl)di-tert-butylphosphine (345mg, 1.156 mmol) and lithium chloride (710mg, 16.73 mmol) are purged with argon. 1-23.3 (2.29g, 6.44 mmol) dissolved in DMF (15 mL) and triethylamine are added and stirred at 80°C overnight. The reaction mixture is concentrated, then diluted with dichlormethane and washed with 5%> K2C03-solution. The organic layer is dried and concentrated. The crude product is purified by reversed phase HPLC. Yield 33%, m/z 441 [M+H]+, rt 1.23 min, LC-MS Method V011 S01. |
33% | With triethylamine; lithium chloride; bis(dibenzylideneacetone)-palladium(0); johnphos In N,N-dimethyl-formamide at 80℃; Inert atmosphere; | Step 4 Synthesis of methyl(E)-2-(benzyloxycarbonylamino)-3-[4-(1,4-dimethyl-4-piperidyl)-2-fluoro-phenyl]prop-2-enoate (R42) 2-benzyloxycarbonylamino-acrylicacidmethylester (2.274 g, 9.67 mmol), bis(dibenzylideneacetone) palladium (0) (295 mg, 0.32 mmol), (2-biphenylyl)di-tert-butylphosphine (345 mg, 1.156 mmol) and lithium chloride (710 mg, 16.73 mmol) are purged with argon. I-23.3 (2.29 g, 6.44 mmol) is dissolved in DMF (15 mL) and triethylamine are added and stirred at 80° C. overnight. The reaction mixture is concentrated, then diluted with dichlormethane and washed with 5% K2CO3-solution. The organic layer is dried and concentrated. The crude product is purified by reversed phase HPLC. Yield 33%, m/z 441 [M+H]+, rt 1.23 min, LC-MS Method V011_S01. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.95 g | With sodium fluoride In toluene Reflux; | A 3-neck flask containing methyl 2-(benzyloxycarbonylamino)acrylate (6.80 g, 28.9 mmol), sodium fluoride (0.121 g, 2.89 mmol) and toluene (150 mL) was heated to gentle reflux. A solution of trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)acetate (14.24 mL, 72.3 mmol) in toluene (150 mL) was added dropwise over 4 h. The reaction mixture was heated for another 3 hours, then cooled to rt, quenched with sat. Na2CO3 at 0 °C. The separated aqueous layer was extracted with EtOAc. The combined organic layer was washed with brine, dried over Mg504, filtered, concentrated in vacuo. The residue was purified by silica gelchromatography to afford Cap W-10 Step a (7.95 g,). ‘H NMR (400 MHz, CDC13) ppm 7.32 - 7.47 (5 H, m), 5.54 (1 H, br. s.), 5.17 (2 H, s), 3.68 - 3.89 (3 H, m), 2.56 - 2.84 (1 H, m), 1.98 (1 H, br. s.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Stage #1: dimethylphenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)silane With o-phenylenebis(diphenylphosphine); potassium <i>tert</i>-butylate; copper(l) chloride In tetrahydrofuran for 0.166667h; Sealed tube; Stage #2: methyl 2-(benzyloxycarbonylamino)acrylate In tetrahydrofuran; methanol at 50℃; for 20h; Sealed tube; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With (S)-[1,1']-binaphthalenyl-2,2'-diol; tin(IV) chloride In dichloromethane at 20℃; for 4.5h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: p-chloroaniline hydrochloride With sodium nitrite In water; acetone for 0.25h; Stage #2: methyl 2-(benzyloxycarbonylamino)acrylate In water; acetone at 0℃; for 0.333333h; Stage #3: With ferrocene In water; acetone at 0℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With silver(I) acetate; palladium diacetate; N-acetylglycine at 80℃; for 36h; Sealed tube; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With silver(I) acetate; palladium diacetate; N-acetylglycine at 75℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: 3-Methylacetophenone With 2-(2,3-dihydroxypropoxy)-4,5-dimethoxybenzonitrile; toluene-4-sulfonic acid In toluene for 12h; Reflux; Stage #2: methyl 2-(benzyloxycarbonylamino)acrylate With 1,1,1,3',3',3'-hexafluoro-propanol; C4H6O4; silver(I) acetate; palladium diacetate In water at 80℃; for 24h; Stage #3: In water at 80℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With 3,6‐di‐tert‐butyl‐9‐mesityl‐10‐phenylacridin‐10‐ium tetrafluoroborate; sodium 2,2,2-trifluoroacetate In methanol; dichloromethane at 30℃; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With C115H106CoN8O4; caesium carbonate In chlorobenzene at 4℃; for 12h; Schlenk technique; Inert atmosphere; Sealed tube; Overall yield = 85 percent; Optical yield = 50 percent de; | 6.1. Supplemental Experimental Procedure for [Co(Por)]-Catalyzed Cyclopropanation General procedure: An oven-dried Schlenk tube was charged with 1.0 equivalent of olefin (0.1 mmol), 1.2equivalents of hydrazone (0.12 mmol), [Co(Por)] (2 mol %) and 2.4 equivalents of Cs2CO3(0.24 mmol). The Schlenk tube was then evacuated and back filled with nitrogen for 3times. The Teflon screw cap was replaced with a rubber septum, and PhCl (1 mL) wasadded. The Schlenk tube was then purged with nitrogen for 30 s and the rubber septum wasreplaced with a Teflon screw cap. The mixture was stirred at 4 C. After 12 h, the reactionmixture was filtered through a plug of silica and then concentrated in vacuo. The residuewas purified via a flash chromatography to afford the compound as a mixture of Z/Ediastereomers. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With tetrakis(trifluoroacetato)rhodium(II) In chloroform at 80℃; Inert atmosphere; diastereoselective reaction; |
[ 70396-37-1 ]
Methyl 2-(((benzyloxy)carbonyl)amino)but-2-enoate
Similarity: 0.92
[ 156174-28-6 ]
Methyl 2-(((benzyloxy)carbonyl)amino)-4-methylpent-2-enoate
Similarity: 0.87
[ 176794-74-4 ]
(Z)-Methyl 3-([1,1'-biphenyl]-4-yl)-2-(((benzyloxy)carbonyl)amino)acrylate
Similarity: 0.85
[ 70396-37-1 ]
Methyl 2-(((benzyloxy)carbonyl)amino)but-2-enoate
Similarity: 0.92
[ 156174-28-6 ]
Methyl 2-(((benzyloxy)carbonyl)amino)-4-methylpent-2-enoate
Similarity: 0.87
[ 176794-74-4 ]
(Z)-Methyl 3-([1,1'-biphenyl]-4-yl)-2-(((benzyloxy)carbonyl)amino)acrylate
Similarity: 0.85
[ 70396-37-1 ]
Methyl 2-(((benzyloxy)carbonyl)amino)but-2-enoate
Similarity: 0.92
[ 156174-28-6 ]
Methyl 2-(((benzyloxy)carbonyl)amino)-4-methylpent-2-enoate
Similarity: 0.87
[ 176794-74-4 ]
(Z)-Methyl 3-([1,1'-biphenyl]-4-yl)-2-(((benzyloxy)carbonyl)amino)acrylate
Similarity: 0.85
[ 70396-37-1 ]
Methyl 2-(((benzyloxy)carbonyl)amino)but-2-enoate
Similarity: 0.92
[ 156174-28-6 ]
Methyl 2-(((benzyloxy)carbonyl)amino)-4-methylpent-2-enoate
Similarity: 0.87
[ 176794-74-4 ]
(Z)-Methyl 3-([1,1'-biphenyl]-4-yl)-2-(((benzyloxy)carbonyl)amino)acrylate
Similarity: 0.85
[ 70396-37-1 ]
Methyl 2-(((benzyloxy)carbonyl)amino)but-2-enoate
Similarity: 0.92
[ 156174-28-6 ]
Methyl 2-(((benzyloxy)carbonyl)amino)-4-methylpent-2-enoate
Similarity: 0.87
[ 176794-74-4 ]
(Z)-Methyl 3-([1,1'-biphenyl]-4-yl)-2-(((benzyloxy)carbonyl)amino)acrylate
Similarity: 0.85
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :