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. : | 32559-18-5 | MDL No. : | MFCD00192316 |
Formula : | C7H14ClNO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | APCHKWZTSCBBJX-UHFFFAOYSA-N |
M.W : | 179.64 | Pubchem ID : | 13246231 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.86 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 48.62 |
TPSA : | 38.33 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.61 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 1.1 |
Log Po/w (WLOGP) : | 0.72 |
Log Po/w (MLOGP) : | 0.69 |
Log Po/w (SILICOS-IT) : | 0.9 |
Consensus Log Po/w : | 0.68 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.51 |
Solubility : | 5.49 mg/ml ; 0.0306 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.5 |
Solubility : | 5.71 mg/ml ; 0.0318 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.14 |
Solubility : | 13.0 mg/ml ; 0.0723 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.98 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
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 |
---|---|---|
98% | Stage #1: at -30℃; Stage #2: at 0 - 20℃; for 15 h; |
Synthesis of methyl piperidine-2-carboxylate hydrochloride Into a 3000 mL 3-necked round-bottom flask was placed CH3OH (1300 mL). The temperature was cooled to -30° C. To the above was added SOCl2 (280 mL) dropwise with stirring, while the temperature was maintained at -30° C. To the above was added piperidine-2-carboxylic acid (100 g, 766.49 mmol) in several batches, while cooling to a temperature of 0° C. The resulting solution was allowed to react, with stirring, for 15 hours while the temperature was maintained at room temperature. The reaction progress was monitored by TLC (CH3OH adding several drops of NH3 H2O). The mixture was concentrated by evaporation under vacuum using a rotary evaporator. To this was added toluene (100 mL), the temperature was maintained at reflux. The mixture was concentrated by evaporation under vacuum using a rotary evaporator. The steps of adding toluene and concentrated were repeated twice. This resulted in 137 g (98percent) of methyl piperidine-2-carboxylate hydrochloride as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Synthesis of methyl piperidine-2-carboxylate hydrochloride Into a 3000 mL 3-necked round-bottom flask was placed CH3OH (1300 mL). The temperature was cooled to -30 C. To the above was added SOCl2 (280 mL) dropwise with stirring, while the temperature was maintained at -30 C. To the above was added piperidine-2-carboxylic acid (100 g, 766.49 mmol) in several batches, while cooling to a temperature of 0 C. The resulting solution was allowed to react, with stirring, for 15 hours while the temperature was maintained at room temperature. The reaction progress was monitored by TLC (CH3OH adding several drops of NH3 H2O). The mixture was concentrated by evaporation under vacuum using a rotary evaporator. To this was added toluene (100 mL), the temperature was maintained at reflux. The mixture was concentrated by evaporation under vacuum using a rotary evaporator. The steps of adding toluene and concentrated were repeated twice. This resulted in 137 g (98%) of methyl piperidine-2-carboxylate hydrochloride as a white solid. | |
With thionyl chloride; at 0 - 80℃; for 12h; | Add 2-piperidinecarboxylic acid (134 mmol) to a 250 ml round bottom flask, and add about 50 ml of methanol to stir and dissolve.The system was placed in an ice bath at 0 C, and thionyl chloride (200 mmol) was slowly added dropwise using a constant pressure dropping funnel.After the completion of the dropwise addition, the mixture was heated to 80 C and condensed and refluxed for 12 hours, and the TLC was traced until the reaction was completed. After the reaction is complete, concentrate,The solid will be precipitated, suction filtered, rinsed with a small amount of methanol, and the filter cake is collected and dried in an oven.The hydrochloride salt of methyl 2-piperidinecarboxylate as a white solid was obtained, which was used directly in the next step. | |
With thionyl chloride; at 0 - 80℃; for 12.5h; | General procedure: To a solution of alpha-amino acid 1 (0.134 mmol) in methanol (50 ml) was slowly added dropwise thionyl chloride (0.200 mmol), which was stired at ice bath (0 C) for 30 min, and then the mixture was heated to 80 C for 12 h reaction, and monitored by TLC. After the completion of reaction, the reaction solution was concentrated, filtered and washed twice with CH2Cl2 to obtain the crude amino-acid ester hydrochlorides 2, which were used for the next reaction without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With dmap; triethylamine; In dichloromethane; at 10 - 30℃; for 16h; | Embodiment 47 (E)-1-(2,6-Dimethoxy-4-(2-(2-methylbiphenyl-3-yl)vinyl)benzyl)-2-(hydrox ymethylpiperidine-2-carboxylic acid 47 Synthetic route Synthesis of compound 47-e Methyl 2-piperidinecarboxylate (1.0g, 5.57mmol) was dissolved in dichloromethane (30mL), then di-tert-butyl dicarbonate (3.04g, 13.92mmol), 4-dimethylaminopyridine (0.68g, 5.57mmol) and triethylamine (1.70g, 16.71mmol) were successively added. The reaction solution was stirred at room temperature for 16 hours, then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1 to 3:1) to give compound 47-e (1.364g, yield 98%). 1H NMR (500 MHz, CDCl3) delta: 4.90-4.73 (m, 1H), 4.03-3.91 (m, 1H), 3.73 (s, 3H), 2.97-2.86 (m, 1H), 2.24-2.17 (m, 1H), 1.69-1.62 (m, 3H), 1.47-1.44 (s, 9H), 1.31-1.21 (m, 2H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; for 16h; | To a stirred solution of methyl pipecolate hydrochloride (1 g, 5.57 mmol) in THF (10 ml) was added phenothiazine carbonyl chloride (1.457 g, 5.57 mmol) followed by diisopropylethylamine (2.02 ml, 11.68 mmol). The resulting solution was stirred for 16 h before being partitioned between ethyl acetate and aq. sat. NH4Cl. The organic layer was washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by flash chromatography (15% ethyl acetate in hexane) to afford the sub-title compound as a colorless oil which crystallized upon standing (1.823 g, 89%): 1H NMR (400 MHz, CDCl3) delta 1.13-1.48 (3H, m), 2.57-2.69 (2H, m), 2.16 (1H, m), 3.00 (1H, m), 3.74 (4H, s+m), 5.00 (1H, m), 7.11 (2H, t), 7.22-7.34 (4H, m), 7.76 (2H, d); 13C NMR (100 MHz, CDCl3) delta 21.3 (CH2), 24.8 (CH2), 27.3 (CH2), 44.9 (CH2), 52.5 (CH3), 55.9 (CH), 122.8 (CH), 125.5 (CH), 127.8 (CH), 128.0 (CH), 129.2 (C), 141.7 (C), 158.4 (C), 172.2 (C) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.6% | With sodium tris(acetoxy)borohydride; triethylamine; In 1,2-dichloro-ethane; at 20℃; for 1.5h; | Methyl pipecolinate hydrochloride (9.0 g, 50 mmol) was mixed with pyridine-2- carbaldehyde (5.4 g, 50 mmol) and triethylamine (5.05 g, 50 mmol) in dichloroethane (180 mL) at room temperature. Sodium triacetoxyborohydride (14.8 g, 70 mmol) was added in one portion. After the reaction mixture was stirred at room temperature for 1.5 h, saturated sodium carbonate was added. Then the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried with sodium sulfate, filtered and concentrated to give 10.9 g (93.6%) of the title compound as a pale brown [OIL. LH NMR (CDC13), 6] (ppm): 8.53 (d, 1H), 7.65 (td, 1H), 7.49 (d, 1H), 7.14 (t, 1H), 3.89 (d, 1H), 3.73 (s, 3H), 3. 68 (d, 1H), 3.25 (dd, 1H), 2.97 (m, 1H), 2.25 (m, [1H),] 1.85 (m, 2H), 1.30-1. 76 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; at 25℃; for 18h; | (a) N-Methylpiperidine-2-carboxamide.; To methyl pipecolinate hydrochloride (5.0 g, 28 mmol, Aldrich) was added methylamine (20 mL, 40 wt. % solution in H2O, Aldrich). The mixture was stirred at 25 C. for 18 h and then evaporated under reduced pressure. The residue was dried in vacuo to give the crude title compound, which was used in the next step without additional purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; | 1-(2-Oxo-2-thiophen-2-yl-acetyl)piperidine-2-carboxylic acid N'-(6-methyl-4-trifluoromethyl-pyridin-2-yl)-hydrazide A solution of methyl pipecolinate hydrochloride (7.2 g, 40 mmol) in dry DCM (100 mL) and TEA (8.3 g) was cooled to 0 C. The slurry was stirred for 1 h. Methyl oxalyl chloride was added. The mixture was stirred at 0 C. for 2 h. Water was added, and the organic phase was washed with a NaHCO3 solution, dried with MaSO4. Evaporation of the solvent and drying in vacuum gave a reddish oil; 9.1 g (99%); MS (m/z) 252 (M+Na). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogenchloride; triethylamine; In hexane; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; ethyl acetate; | Method F (S)-1-(2 Chlorobenzyloxycarbonyl)-piperidine-2-carboxylic acid methyl ester To a vigorously stirred solution of (S)-pipecolic acid methyl ester hydrochloride (500 mg, 2.79 mmol) in dry DCM (10 mL) cooled in an ice-bath, was added dropwise Et3N (705 mg, 6.96 mmol) followed by 2-chlorobenzyl chloroformate (made from 2-chlorobenzyl alcohol using the method described in J. Med. Chem., 1998, 41, 1315-1343) (857 mg, 4.18 mmol). The resulting suspension was stirred at 0 C. for a further 0.75 h, diluted with ethyl acetate (30 mL) and poured into 1.0-M HCl (30 mL). The organic layer was separated and washed sequentially with 1.0-M HCl (20 mL), aq.NaHCO3 (20 mL) and brine (20 mL). The organic layer was then dried (NaSO4), filtered and concentrated under reduced pressure to give a colorless oil. The oil was purified by column chromatography (15% ethyl acetate in hexane) to give the title compound as a colorless viscous oil (824 mg, 95%): 1H NMR (400 MHz, CDCl3) 1.2-1.4 (1H, m), 1.4-1.6 (1H, m), 1.6-1.8 (3H, m), 2.2-2.3 (1H, m), 2.9-3.2 (1H, m), 3.7-3.8 (3H, m), 4.0-4.2 (1H, m), 4.8-5.0 (1H, m), 5.2-5.4 (2H, m), 7.2-7.3 (2H, m), 7.3-7.5 (2H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | With triethylamine; In tetrahydrofuran; methyl piperidine-2-(RS)-carboxylate HCl salt; | Step 2 Triethylamine (0.59 ml, 4.22 mmol) was added dropwise to a mixture of 4-(4-chlorophenyl)piperazinesulfamoyl chloride (0.56 g, 1.9 mmol), [prepared as described in Step 1 above] and methyl piperidine-2-(RS)-carboxylate HCl salt (0.38 g, 2.11 mmol) in tetrahydrofuran (15 ml) and the reaction mixture was heated at reflux. After 19 h, additional amounts of methyl piperidine-2-carboxylate HCl salt (189 mg) and triethylamine (0.15 ml) were added and the heating was continued. After 5 h, the reaction mixture was cooled, diluted with methylene chloride (40 ml), and washed with 10% citric acid, water, and brine, and dried over MgSO4. The organics were removed in vacuo and the residue was chromatographed (SiO2, 10-35% ethyl acetate/hexane) to yield methyl 1-[4-(4-chlorophenyl)piperazine-1-sulfonyl]piperidine-2-(RS)-carboxylate as a colorless glass (21%). |
21% | With triethylamine; In tetrahydrofuran; methyl piperidine-2-(RS)-carboxylate HCl salt; | Step 2 Triethylamine (0.59 ml, 4.22 mmol) was added dropwise to a mixture of 4-(4chlorophenyl)piperazinesulfamoyl chloride (0.56 g, 1.9 mmol), [prepared as described in Step 1 above] and methyl piperidine-2-(RS)-carboxylate HCl salt (0.38 g, 2.11 mmol) in tetrahydrofuran (15 ml) and the reaction mixture was heated at reflux. After 19 h, additional amounts of methyl piperidine-2-carboxylate HCl salt (189 mg) and triethylamine (0.15 ml) were added and the heating was continued. After 5 h, the reaction mixture was cooled, diluted with methylene chloride (40 ml), and washed with 10% citric acid, water, and brine, and dried over MgSO4. The organics were removed in vacuo and the residue was chromatographed (SiO2, 10-35% ethyl acetate/hexane) to yield methyl 1-[4-(4-chlorophenyl)piperazine-1-sulfonyl]piperidine-2-(RS)-carboxylate as a colorless glass (21%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 19 (D)-Cyclohexylglycylpiperidine-2-carboxylic acid 6-amidino-3-picolylamide: The required product was obtained by the above procedure starting from Boc-(D)-cyclohexylglycine and methyl (L)-piperidine-2-carboxylate hydrochloride. Acetate: white amorphous powder; FAB-MS (M+H)+: 401. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; triethylamine; In dichloromethane; | (a) To a stirred solution of 7.36 ml (85 mmol) of chlorosulfonyl isocyanate in 180 ml of methylene chloride was added phenylmethanol (8.82 ml, 85 mmol) at 0 C. over a period of 35 minutes. After stirring the above solution for 2 hours at this temperature, a solution of 16.65 g (93 mmol) of 2-piperidinecarboxylic acid methyl ester hydrochloride in methylene chloride (500 mL) containing triethylamine (35.3 ml) was added at 0-5 C., and the resulting mixture was stirred overnight allowing the mixture to warm to room temperature. The reaction mixture was poured into 600 ml of 10% aq. HCl solution, saturated with sodium chloride, and the organic layer was separated. The aqueous layer was extracted with methylene chloride (2*200 ml) and the combined organic layer was washed with brine, dried and concentrated in vacuo to yield 31 g of N-(carbobenzyloxyaminosulfonyl)-2-piperidinecarboxylic acid methyl ester (Formula XIV: R1 =H; R2 and R3 together=--(CH2)4 --; R=CH3) as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A. tetramethyleneglycine methyl ester hydrochloride A solution of 2.5 g alpha-tetramethyleneGly in 30 mL MeOH was saturated with anhydrous HCl and stirred at RT for 60 hours. The solution was concentrated in vacuo and the residue was recrystallized from ether/ethanol to afford 2.4 g pure product. NMR (300 MHz, DMSO-d6) delta 3.77 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 218 Synthesis of Methyl 1-[N-(3,5-Difluorophenylacetyl)-L-alaninyl]piperidine-2-carboxylate Following General Procedure A and using N-(3,5-difluorophenylacetyl)-L-alanine (from Example B2 above) and methyl pipecolinate hydrochloride (Aldrich), the title compound was prepared as a solid (mp=114-118 C.). The reaction was monitored by tlc (Rf=0.71 in 10% MeOH/DCM) and the product was purified by acid/base washes. NMR data was as follows: 1H-nmr (CDCl3): delta=6.95 (dd, J=7.1, 7.1, 7.1 Hz; 1H), 6.81 (d, J=6.1 Hz, 2H), 6.7 (m, 1H), 5.28 (dd, J=5.0 Hz, 12.6, 5.4, 1H), 4.93 (q, J=7.0, 6.9, 7.0 Hz, 1H), 3.75 (s, 1H), 3.70 (s, 3H), 3.50 (s, 2H), 3.2 (m, 1H), 2.27 (d, J=3.5 Hz, 1H), 1.5 (m, 5H), 1.31 (d, J=5.2 Hz, 3H). 13C-nmr (CDCl3): delta=172.8; 172.6; 171.7; 171.6; 169.2; 169.1; 112.9; 112.8; 112.7; 112.6; 103.2; 102.8; 53.0; 52.9; 52.9; 52.7; 46.2; 46.1; 43.9; 43.9; 27.1; 26.8; 25.6; 21.4; 19.9; 18.5. | ||
EXAMPLE 218 Synthesis of Methyl 1-[N-(3,5-Difluorophenylacetyl)-L-alaninyl]piperidine-2-carboxylate Following General Procedure A and using N-(3,5-difluorophenylacetyl)-L-alanine (from Example B2 above) and methyl pipecolinate hydrochloride (Aldrich), the title compound was prepared as a solid (mp=114-118 C.). The reaction was monitored by tlc (Rf=0.71 in 10% MeOH/DCM) and the product was purified by acid/base washes. NMR data was as follows: 1H-nmr (CDCl3): delta=6.95 (dd, J=7.1, 7.1, 7.1 Hz; 1H), 6.81 (d, J=6.1 Hz, 2H), 6.7 (m, 1H), 5.28 (dd, J=5.0 Hz, 12.6, 5.4, 1H), 4.93 (q, J=7.0, 6.9, 7.0 Hz, 1H), 3.75 (s, 1H), 3.70 (s, 3H), 3.50 (s, 2H), 3.2 (m, 1H), 2.27 (d, J=3.5 Hz, 1H), 1.5 (m, 5H), 1.31 (d, J=5.2 Hz, 3H). 13C-nmr (CDCl3): delta=172.8; 172.6; 171.7; 171.6; 169.2; 169.1; 112.9; 112.8; 112.7; 112.6; 103.2; 102.8; 53.0; 52.9; 52.9; 52.7; 46.2; 46.1; 43.9; 43.9; 27.1; 26.8; 25.6; 21.4; 19.9; 18.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2. Synthesis of methyl 1-(2-chloroacetyl)piperidine-2-carboxylate Into a 3000 mL 3-necked round-bottom flask, was placed CH2Cl2 (1500 mL). To this was added Et3N (154.35 g, 1.53 mol). To the mixture was added <strong>[32559-18-5]methyl piperidine-2-carboxylate hydrochloride</strong> (137 g, 739.76 mmol). Then the temperature was cooled to 0 C. This was followed by the addition of a solution of 2-chloroacetyl chloride (86.13 g, 762.62 mmol) in DCM (500 mL), which was added dropwise with stirring, while the temperature maintained at 0 C. The resulting solution was allowed to react, with stirring, for 2 hours while the temperature was maintained at 0 C. in a bath of H2O/ice. The reaction progress was monitored by TLC (CH2Cl2/MeOH=10:1, adding one drop of NH3.H2O). The resulting mixture was washed 1 time with 200 mL of H2O, 1 time with 250 mL of saturated NaHCO3 solution and 1 time with 200 mL of saturated NaCl solution. The mixture was dried over Na2SO4. A filtration was performed. This resulted in methyl 1-(2-chloroacetyl)piperidine-2-carboxylate and the product was directly used by the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 2h; | Pipecolic acid methyl ester hydrochloride (2.33g, 2 eq) was coupled to the resin using BOP (12 mmol, 2 eq) and HOBt (12 mmol, 2 eq), as activating agents in the presence of DIEA (30 mmol, 5 eq). The reaction mixture was allowed to react for 2 hours, and the process was repeated once more. Finally, the resin was washed with DMF, MeOH, and DCM to yield resin ((D), corresponding to the compound of formula (II) wherein X = -NH-CO-, Ri = cyclohexyl and R3 = methyl). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; for 1.5h;Inert atmosphere; | The synthesis of 1 -(6,8-Dimercaptooctanyl) Piperidine-2-Carboxylic Acid was performed by a three step procedure that began with the synthesis of (DL)- pipecolinyl methyl ester lipoic acid from (DL)-pipecolinyl methyl ester and (DL)-alpha- lipoic acid. Briefly, the synthesis of (DL)-pipecolinyl methyl ester lipoic acid was completed by combining (DL)-pipecolinic acid methyl ester and (DL)-alpha-lipoic acid using a suitable coupling reagent, as shown in FIG. 9. The first step of the reaction was carried out under a nitrogen atmosphere. (DL)-alpha-lipoic acid, 0.206 g (1 mM); (DL)-<strong>[32559-18-5]pipecolinic acid methyl ester hydrochloride</strong>, 0.166 g (1 mM); dimethylaminopyridine, 0.122 g (1 mM); and triethylamine, 0.101 g (1 mM, 0.140 ml_) were dissolved in methylene chloride (35 ml_) and were combined in a 100 ml_ round bottom flask. The contents of the flask were stirred well for 5 minutes at room temperature. The coupling reagent EDCI, 0.287 g (1 .5 mM) was added in portions over a period of 1 .5 hours while the contents of the flask were simultaneously stirred. Completion of the reaction was monitored using thin layer chromatography by comparing the disappearance of the starting materials and the formation of the new product as shown in FIG. 10.After stirring overnight, the methylene chloride was evaporated under reduced pressure using a rotary evaporator. The resultant crude product was purified using fluorescent preparative thin layer chromatography with a ratio of 90:5:10 ethylacetate:hexane:methanol. The desired compound band was scraped and the compound was extracted from the band by continuously eluting with ethylacetate (350 ml_). The solvent was evaporated to dryness under a vacuum. A pale yellow, highly viscous liquid was obtained in a 59% yield, and was determined to be (DL)- pipecolinyl methyl ester lipoic acid (Formula (V)). |
59% | Example 6 - Synthesis of 1-(6,8-bis(nitrososulfanyl)octanoyl)piperidine-2- carboxylic acidThe synthesis of 1-(6,8-bis(nitrososulfanyl)octanoyl)piperidine-2-carboxylic acid was performed by a three step procedure. The first step of the procedure is shown in the following schematic representation:1 eq of Dimethylaminopyndine 1 eq of triethylamine 1 5 eq of EDCI (coupling reagent) DichloromethaneThe first step of the procedure began with the synthesis of (DL)-pipecolinyl methyl ester lipoic acid from (DL)-pipecolinyl methyl ester and (DL)-alpha-lipoic acid. Briefly, the synthesis of (DL)-pipecolinyl methyl ester lipoic acid was completed by combining (DL)-pipecolinic acid methyl ester and (DL)-alpha-lipoic acid using a suitable coupling reagent, as shown in the scheme above. The first step of the reaction was carried out under a nitrogen atmosphere. (DL)-alpha-lipoic acid, 0.206 g (1 mM); (DL)-<strong>[32559-18-5]pipecolinic acid methyl ester hydrochloride</strong>, 0.166 g (1 mM); dimethylaminopyndine, 0.122 g (1 mM); and triethylamine, 0.101 g (1 mM, 0.140 ml_) were dissolved in methylene chloride (35 ml_) and were combined in a 100 ml_ round bottom flask. The contents of the flask were stirred well for 5 minutes at room temperature. The coupling reagent EDCI, 0.287 g (1.5 mM) was added in portions over a period of 1.5 hours while the contents of the flask were simultaneously stirred. Completion of the reaction was monitored using thin layer chromatography by comparing the disappearance of the starting materials and the formation of the new product. After stirring overnight, the methylene chloride was evaporated under reduced pressure using a rotary evaporator. The resultant crude product was purified using fluorescent preparative thin layer chromatography with a ratio of 90:5:10 ethylacetate:hexane:methanol. The desired compound band was then scraped and the compound was extracted from the band by continuously eluting with ethylacetate (350 ml_). The solvent was evaporated to dryness under a vacuum. A pale yellow, highly viscous liquid was obtained in a 59% yield, and was determined to be (DL)- pipecolinyl methyl ester lipoic acid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | A solution of methyl pipecolate hydrochloride (8.50 g; 47.31 mmol) in dry methylene chloride (100 mL) was cooled to 0C and treated with triethylamine (10.5 g; 103 mmol; 2.1 eq). After stirring the formed slurry under a nitrogen atmosphere for 15 minutes, a solution of methyl oxalyl chloride (8.50 g; 69.4 mmol) in methylene chloride (75 mL) was added dropwise. The resulting mixture was stirred at 0C for 1,5 hours. After filtering to remove solids, the organic phase was washed with water, dried over MgSO4 and concentrated. The crude residue was purified on a silica gel column, eluting with 50% ethyl acetate in hexane, to obtain 9.34 g (86%) of the product as a reddish oil. Mixture of cis-trans amide rotamers; data for trans rotamer given. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at -70 - 20℃;Inert atmosphere; | Intermediate 16a (1.00 g, 4.165 mmol) is mixed with DCM (60 mL) under nitrogen. The reaction mixture is cooled to -70 C. and a mixture of <strong>[32559-18-5]piperidine-2-carboxylic acid methyl ester hydrochloride</strong> (0.760 g, 4.23 mmol) and DIPEA (0.712 mL, 4.16 mmol) in DCM (20 mL) is added slowly. The reaction mixture is allowed to reach room temperature slowly followed by addition of aqueous potassium hydrogensulfate solution (80 mL) and stirring for 15 min. The phases are separated and the organic phase is concentrated in vacuo to give the product as an oil that is used for the next step without further purification. | |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at -70 - 20℃;Inert atmosphere; | Intermediate 16a (1 .00 g, 4.165 mmol) is mixed with DCM (60 mL) under nitrogen. The reaction mixture is cooled to -70C and a mixture of <strong>[32559-18-5]piperidine-2-carboxylic acid methyl ester hydrochloride</strong> (0.760 g, 4.23 mmol) and DIPEA (0.712 mL, 4.16 mmol) in DCM (20 mL) is added slowly. The reaction mixture is allowed to reach room temperature slowly followed by addition of aqueous potassium hydrogensulfate solution (80 mL) and stirring for 15 min. The phases are separated and the organic phase is concentrated in vacuo to give the product as an oil that is used for the next step without further purification |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With triethylamine; In toluene; at 110℃; for 24h;Reflux; | General procedure: Oxazolidines 4, 6, 8, 10, 13, and 15; General ProcedureTo a solution of the corresponding amino ester hydrochloride (0.43mmol) in toluene (2 mL), Et3N (if needed) (1.5 equiv, 90 muL, 0.645mmol, see text) and paraformaldehyde (15 equiv, 306 mg, 6.45mmol) were added. The resulting mixture was refluxed at 111 Cfor 24 h or irradiated with microwaves (111 C, 30 min). EtOAc (5mL) and H2O (5 mL) were added and the organic phase was separated,dried (MgSO4), and evaporated to obtain the pure heterocyclein good chemical yields (see also text). The yields given below forthe products are for the thermal reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; | General procedure: A mixture of (R)-tert-butyl 2-(pyrrolidin-2-ylmethoxy)acetate hydrochloride (17) (30-100 mg, 0.1-0.4 mmol), either acetylthioacetic acid, 3-(acetylthio)propanoic acid or 4-(acetylthio)butanoic acid(1.5 eq.), DIPEA (0.2-0.7 mL, 1.2-4.1 mmol) and HBTU (69-230 mg, 0.2-0.6 mmol) in THF (0.6-1mL) was stirred for two days at room temperature. The solvent was then evaporated under reducedpressure and ethyl acetate (3 mL) was added to the crude product. The mixture was washed withwater (3 mL) and brine (2×3 mL), dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography using ethyl acetate/petroleum ether (1:2) to give the desiredproducts 18-20 as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; | General procedure: A mixture of <strong>[32559-18-5]methyl piperidine-2-carboxylate hydrochloride</strong> (0.5 g, 2.8 mmol), either acetylthioaceticacid, 3-(acetylthio)propanoic acid or 4-(acetylthio)butanoic acid (1.5 eq.), DIPEA (2.4 mL, 14 mmol)and HBTU (1.6 g, 4.2 mmol) in THF (11 mL) was stirred overnight at room temperature. The solventwas then evaporated under reduced pressure and ethyl acetate (20 mL) was added to the crudeproduct. The mixture was washed with water (20 mL) and brine (2×20 mL), dried (Na2SO4) andconcentrated in vacuo. The crude product was purified by column chromatography (ethylacetate/petroleum ether (30-50%) to give the products as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59%; 22% | With triethylamine; In toluene; at 70℃; for 17h; | General procedure: To a solution of the pipecolic acid methyl ester hydrochloride 1 (40mg, 0.22 mmol) in toluene (1 mL), Et3N (30.5 muL, 0.22 mmol, 1 equiv), the corresponding aldehyde (0.22 mmol, 1 equiv) and the dipolarophile (0.22 mmol, 1 equiv) were added. The resulting mixture was stirred at 70 C for 17 h. EtOAc (5 mL) and H2O (5 mL) were added and the organic phase was separated, dried (MgSO4), and evaporated to afford the crude heterocycle, which was purified by flash chromatography(silica gel) in the chemical yields reported in the text. Methyl (3aS*,4S*,9aR*,9bR*)-2-Methyl-1,3-dioxo-4-[(E)-styryl]decahydro-9aH-pyrrolo[3,4-a]indolizine-9a-carboxylate (endo-2)Yield: 36 mg (59%); colorless prisms; mp 134-135 C (Et2O).IR (neat): 1734, 1698, 1213 cm-1.1H NMR (300 MHz, CDCl3): delta = 1.18 (dt, J = 13.3, 3.5 Hz, 1 H,NCH2CH2CH2), 1.27-1.48 (m, 1 H, NCH2CH2CH2), 1.45-1.63 (m, 2 H,NCH2CH2), 1.74 (dt, J = 13.2, 3.4 Hz, 1 H, CCH2), 2.48 (ddd, J = 13.2, 2.9,1.4 Hz, 1 H, CCH2), 2.81, 2.84 (2 × d, J = 2.7 Hz, 2 H, NCH2), 3.01 (s, 3 H,NCH3), 3.25 (dd, J = 8.0, 7.9 Hz, 1 H, NCHCH), 3.35 (d, J = 7.9 Hz, 1 H,CCH), 3.76 (s, 3 H, OCH3), 4.18 (dd, J = 9.2, 8.0 Hz, 1 H, NCH), 5.88 (dd,J = 15.6, 9.2 Hz, 1 H, PhCHCH), 6.68 (d, J = 15.6 Hz, 1 H, PhCH), 7.22-7.35 (m, 3 H, ArH), 7.36-7.45 (m, 2 H, ArH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20%; 55% | With triethylamine; In toluene; at 70℃; for 17h; | General procedure: To a solution of the pipecolic acid methyl ester hydrochloride 1 (40mg, 0.22 mmol) in toluene (1 mL), Et3N (30.5 muL, 0.22 mmol, 1 equiv), the corresponding aldehyde (0.22 mmol, 1 equiv) and the dipolarophile (0.22 mmol, 1 equiv) were added. The resulting mixture was stirred at 70 C for 17 h. EtOAc (5 mL) and H2O (5 mL) were added and the organic phase was separated, dried (MgSO4), and evaporated to afford the crude heterocycle, which was purified by flash chromatography(silica gel) in the chemical yields reported in the text. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With triethylamine; In toluene; at 70℃; for 17h; | General procedure: To a solution of the pipecolic acid methyl ester hydrochloride 1 (40mg, 0.22 mmol) in toluene (1 mL), Et3N (30.5 muL, 0.22 mmol, 1 equiv), the corresponding aldehyde (0.22 mmol, 1 equiv) and the dipolarophile (0.22 mmol, 1 equiv) were added. The resulting mixture was stirred at 70 C for 17 h. EtOAc (5 mL) and H2O (5 mL) were added and the organic phase was separated, dried (MgSO4), and evaporated to afford the crude heterocycle, which was purified by flash chromatography(silica gel) in the chemical yields reported in the text. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With triethylamine; In toluene; at 70℃; for 17h; | General procedure: To a solution of the pipecolic acid methyl ester hydrochloride 1 (40mg, 0.22 mmol) in toluene (1 mL), Et3N (30.5 muL, 0.22 mmol, 1 equiv), the corresponding aldehyde (0.22 mmol, 1 equiv) and the dipolarophile (0.22 mmol, 1 equiv) were added. The resulting mixture was stirred at 70 C for 17 h. EtOAc (5 mL) and H2O (5 mL) were added and the organic phase was separated, dried (MgSO4), and evaporated to afford the crude heterocycle, which was purified by flash chromatography(silica gel) in the chemical yields reported in the text. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17%; 55% | With triethylamine; In toluene; at 70℃; for 17h; | General procedure: To a solution of the pipecolic acid methyl ester hydrochloride 1 (40mg, 0.22 mmol) in toluene (1 mL), Et3N (30.5 muL, 0.22 mmol, 1 equiv), the corresponding aldehyde (0.22 mmol, 1 equiv) and the dipolarophile (0.22 mmol, 1 equiv) were added. The resulting mixture was stirred at 70 C for 17 h. EtOAc (5 mL) and H2O (5 mL) were added and the organic phase was separated, dried (MgSO4), and evaporated to afford the crude heterocycle, which was purified by flash chromatography(silica gel) in the chemical yields reported in the text. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11%; 70% | With triethylamine; In toluene; at 70℃; for 17h; | General procedure: To a solution of the pipecolic acid methyl ester hydrochloride 1 (40mg, 0.22 mmol) in toluene (1 mL), Et3N (30.5 muL, 0.22 mmol, 1 equiv), the corresponding aldehyde (0.22 mmol, 1 equiv) and the dipolarophile (0.22 mmol, 1 equiv) were added. The resulting mixture was stirred at 70 C for 17 h. EtOAc (5 mL) and H2O (5 mL) were added and the organic phase was separated, dried (MgSO4), and evaporated to afford the crude heterocycle, which was purified by flash chromatography(silica gel) in the chemical yields reported in the text. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In toluene; at 70℃; for 17h; | General procedure: To a solution of the pipecolic acid methyl ester hydrochloride 1 (40mg, 0.22 mmol) in toluene (1 mL), Et3N (30.5 muL, 0.22 mmol, 1 equiv), the corresponding aldehyde (0.22 mmol, 1 equiv) and the dipolarophile (0.22 mmol, 1 equiv) were added. The resulting mixture was stirred at 70 C for 17 h. EtOAc (5 mL) and H2O (5 mL) were added and the organic phase was separated, dried (MgSO4), and evaporated to afford the crude heterocycle, which was purified by flash chromatography(silica gel) in the chemical yields reported in the text. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With triethylamine; In toluene; at 70℃; for 17h; | General procedure: To a solution of the pipecolic acid alkyl ester hydrochloride 1 (0.22mmol) in toluene (1 mL), Et3N (30.5 muL, 0.22 mmol, 1 equiv), the corresponding aldehyde (0.22 mmol, 1 equiv) and the dipolarophile (0.22 mmol, 1 equiv) were added. The resulting mixture was stirred at 70 C for 17 h. EtOAc (5 mL) and H2O (5 mL) were added and the organic phase was separated, dried (MgSO4), and evaporated to afford the crude product which was purified by flash chromatography (silica gel). Methyl (3aS*,4R*,9aR*,9bR*)-1,3-Dioxo-4-phenyloctahydro-3H,9aH-furo[3,4-a]indolizine-9a-carboxylate (endo-12)Yield: 20 mg (27%); yellow sticky oil.IR (neat): 2927, 2856, 1781, 1733, 1209, 922, 734 cm-1.1H NMR (300 MHz, CDCl3): delta = 1.39-1.53 (m, 2 H, NCHCHCH2), 1.55-1.65 (m, 1 H, NCH2CH2), 1.83 (dt, J = 13.8, 3.5 Hz, 1 H, NCH2CH2), 1.96(td, J = 13.4, 3.9 Hz, 1 H, CCH2), 2.45-2.55 (m, 1 H, CCH2), 2.65 (dd, J =11.9, 4.3 Hz, 1 H, NCH2), 2.78 (td, J = 11.9, 3.3 Hz, 1 H, NCH2), 3.61 (dd,J = 9.4, 8.3 Hz, 1 H, PhCHCH), 3.69 (d, J = 8.3 Hz, 1 H, CCHCO), 3.79 (s, 3H, OCH3), 4.75 (d, J = 9.4 Hz, 1 H, PhCH), 7.22-7.28 (m, 2 H, ArH), 7.29-7.40 (m, 3 H, ArH).13C NMR (75 MHz, CDCl3): delta = 21.4 (NCH2CH2CH2), 24.6 (NCH2CH2),31.0 (CCH2), 44.1 (NCH2), 49.6 (NCHCHCO), 52.1 (CCHCO), 52.2(OCH3), 67.7 (NCH), 70.9 (CCO2Me), 127.8, 128.6, 128.8, 128.9, 130.2,136.5 (ArC, C=C), 169.0, 169.2 (2 × NCO), 172.9 (CO2Me).MS (EI): m/z = 329 (<1) [M]+, 271 (18), 270 (100), 220 (8), 198 (67).HRMS (DIP): m/z [M - CO2Me]+ calcd for C16H16NO3: 270.1130; found:270.1132. |
[ 41994-45-0 ]
Methyl 2-piperidinecarboxylate
Similarity: 0.98
[ 77034-33-4 ]
Ethyl piperidine-2-carboxylate hydrochloride
Similarity: 0.96
[ 123495-48-7 ]
(S)-Ethyl piperidine-2-carboxylate hydrochloride
Similarity: 0.96
[ 144913-66-6 ]
Methyl 4-hydroxypiperidine-2-carboxylate
Similarity: 0.91
[ 41994-45-0 ]
Methyl 2-piperidinecarboxylate
Similarity: 0.98
[ 77034-33-4 ]
Ethyl piperidine-2-carboxylate hydrochloride
Similarity: 0.96
[ 123495-48-7 ]
(S)-Ethyl piperidine-2-carboxylate hydrochloride
Similarity: 0.96
[ 162698-26-2 ]
Methyl azetidine-2-carboxylate hydrochloride
Similarity: 0.91
[ 41994-45-0 ]
Methyl 2-piperidinecarboxylate
Similarity: 0.98
[ 77034-33-4 ]
Ethyl piperidine-2-carboxylate hydrochloride
Similarity: 0.96
[ 123495-48-7 ]
(S)-Ethyl piperidine-2-carboxylate hydrochloride
Similarity: 0.96
[ 144913-66-6 ]
Methyl 4-hydroxypiperidine-2-carboxylate
Similarity: 0.91
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 :