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CAS No. : | 184429-84-3 | MDL No. : | MFCD24466259 |
Formula : | C14H29NO4Si | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | GPCWVDDNSMMEGI-UHFFFAOYSA-N |
M.W : | 303.47 | Pubchem ID : | 11709260 |
Synonyms : |
|
Num. heavy atoms : | 20 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.86 |
Num. rotatable bonds : | 9 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 83.08 |
TPSA : | 64.63 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) : | -5.77 cm/s |
Log Po/w (iLOGP) : | 3.48 |
Log Po/w (XLOGP3) : | 3.35 |
Log Po/w (WLOGP) : | 3.1 |
Log Po/w (MLOGP) : | 1.43 |
Log Po/w (SILICOS-IT) : | 0.93 |
Consensus Log Po/w : | 2.46 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.24 |
Solubility : | 0.175 mg/ml ; 0.000578 mol/l |
Class : | Soluble |
Log S (Ali) : | -4.38 |
Solubility : | 0.0125 mg/ml ; 0.0000412 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -3.41 |
Solubility : | 0.119 mg/ml ; 0.000392 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 3.93 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-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 |
---|---|---|
92% | Stage #1: With oxalyl dichloride; dimethyl sulfoxide In dichloromethane for 1.33333 h; Inert atmosphere; Cooling with ice Stage #2: With triethylamine In dichloromethane at 20℃; Inert atmosphere |
To a stirring solution of oxalyl chloride (13.6 mL, 0.16 mol) in dry CH2Cl2 (150 mL) at -78°C under N2 was added DMSO (15.2 mL, 0.21 mol) dropwise over 30 min. After complete addition the resulting solution was stirred at -78°C for 1 h. A solution of tert-butyl 3-(rt-butyldimethyl-silyloxy)-2-hydroxypropylcarbamate (32.6 g, 0.1 1 mol) in CH2Cl2 (50 mL) was then added dropwise over 20 min. Stirring was continued for a further 1 hour at which time triethylamine (59.6 mL, 0.43 mol) was added. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature. The reaction mixture was partitioned between water (100 mL) and CH2Cl2 (70 mL) and the aqueous layer was extracted with further CH2Cl2 (2 x 70 mL); the combined organics were dried over Na2SO4 and concentrated under a stream of nitrogen gas. The crude residue was purified over silica gel eluting with 5percent ethylacetate in n-hexane to give tert- butyl 3-(tert-butyldimethylsilyloxy)-2-oxopropylcarbamate (29.8 g, 92percent) as a pale yellow oil. 1H-NMR (300 MHz; CDCl3) ppm: 0.11 (6 H, s), 0.94 (9 H, s), 1.47 (9 H, s), 3.92 (2 H, s), 4.26 (2 H, d, J4.6 Hz), 5.22 (1 H, br s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | To a stirring solution of oxalyl chloride (13.6 mL, 0.16 mol) in dry CH2Cl2 (150 mL) at -78C under N2 was added DMSO (15.2 mL, 0.21 mol) dropwise over 30 min. After complete addition the resulting solution was stirred at -78C for 1 h. A solution of tert-butyl 3-(rt-butyldimethyl-silyloxy)-2-hydroxypropylcarbamate (32.6 g, 0.1 1 mol) in CH2Cl2 (50 mL) was then added dropwise over 20 min. Stirring was continued for a further 1 hour at which time triethylamine (59.6 mL, 0.43 mol) was added. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature. The reaction mixture was partitioned between water (100 mL) and CH2Cl2 (70 mL) and the aqueous layer was extracted with further CH2Cl2 (2 x 70 mL); the combined organics were dried over Na2SO4 and concentrated under a stream of nitrogen gas. The crude residue was purified over silica gel eluting with 5% ethylacetate in n-hexane to give tert- butyl 3-(tert-butyldimethylsilyloxy)-2-oxopropylcarbamate (29.8 g, 92%) as a pale yellow oil. 1H-NMR (300 MHz; CDCl3) ppm: 0.11 (6 H, s), 0.94 (9 H, s), 1.47 (9 H, s), 3.92 (2 H, s), 4.26 (2 H, d, J4.6 Hz), 5.22 (1 H, br s). | |
88.7% | To a solution of (COCl)2 (103.11 mmol, 9.03 mL) in DCM (250 mL) at - 78 C under N2 was added DMSO (161.26 mmol, 12.60 mL) in DCM (30 mL) dropwise over 30 min. After addition, the solution was stirred at -78 C for lh. A solution of compound 33A (21 g, 68.74 mmol) in DCM (80 mL) was then added dropwise over 30 min, the solution was stirred at -78 C for lh, then TEA (301.75 mmol, 42.00 mL) was added, the mixture was allowed to warm to 10 C and stirred lh. The reaction mixture was partitioned between water (200 mL) and DCM (50 mL), the aqueous layer was extracted with DCM (80 mL x 2), and the organic layers were washed with brine (150 mL), dried over Na2S04, filtered and concentrated to give a residue. The residue was purified by flash silica gel chromatography (ISCO; 220 g SepaFlash Silica Flash Column, Eluent of 0 ~ 10% Ethyl acetate/Petroleum ether gradient 100 mL/min). Compound 12B (18.5 g, yield: 88.7%) as colorless oil was obtained. 1H NMR (400MHz, CDCb) d 5.20 (br s, 1H), 4.29 - 4.20 (m, 4H), 1.45 (s, 9H), 0.92 (s, 9H), 0.13 - 0.05 (m, 6H). | |
64% | Oxalyl chloride (18.5 mL, 0.21 mmol, 1.5 eq) under nitrogen.Dissolved in dichloromethane (250 mL). The temperature was lowered to -78 C, and DMSO (21 mL, 0.28 mol, 2.0 eq) was added dropwise, and the mixture was kept for 1 hour.tert-Butyl (3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl)carbamate (44 g, 0.14 mol, 1.0 eq) was dissolved in dichloromethane (50 mL)Slowly drip into the reaction system. After the drop, continue to keep warm for 1 hour.Triethylamine (81 mL, 0.56 mmol, 4.0 eq) was added dropwise.After the addition is completed, slowly rise to room temperature.After TLC detection, after completion of the reaction, water (400 mL) was added, and the aqueous phase was extracted three times with dichloromethane. The organic phase was combined, dried and concentrated. The crude product was purified by silica gel column chromatography (100-200 mesh silica gel, petroleum ether / acetic acid The ester was purified to give an oily viscous liquid (28 g, yield: 64%). |
40 g | DMSO (25.6 g, 327 mmol) was added dropwise to a solution of oxalyl chloride (31.2 g, 246 mmol) in DCM (500 mL) at -78 C and the reaction stirred at -78C for an additional 1 h. A solution of /er/-butyl (3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl)carbamate (50 g, 164 mmol) in DCM (100 mL) was then added dropwise at -78 C and stirred at -78C for an additional 1 h. Et3N (82.8 g, 818 mmol) was added dropwise at -78 C and the reaction warmed to room temperature. The mixture was poured into water (500 ml) and extracted with DCM (2 x 1000 mL). The combined organics were dried (Na2S04), filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel (2% ethyl acetate in petroleum ether) gave tert- butyl (3 -((fert-butyl dimethyl silyl)oxy)-2-oxopropyl)carbamate (40 g, 81%) as a yellow oil. 1H NMR (400 MHz, CDCI3) d 5.08 (br s, 1H), 4.21-4.02 (m, 4H), 1.41 (s, 9H), 0.86 (s, 9H), 0.04 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In ethyl acetate; for 2h;Reflux; | A stirred mixture of (R)-6,8-difluorochroman-3-ylamine hydrochloride (0.22 g, 1.0 mmol), <strong>[184429-84-3][3-(tert-butyldimethylsilanyloxy)-2-oxopropyl]carbamic acid tert-butyl ester</strong> (0.33 g, 1.1 mmol), potassium thiocyanate (0.11 g, 1.1 mmol) and acetic acid (0.3 mL, 5.0 mmol) in ethyl acetate (3 mL) was refluxed for 2 hours, cooled to room temperature, then washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by the column chromatography over silica gel using ethyl acetate-petroleum ether mixture as eluent. The resulting oil (0.23 g) was dissolved in ethyl acetate (2 ml), whereupon 2M HCl solution in ethyl acetate was added (2 mL, 4 mmol) and the mixture was stirred for 2 hours at room temperature. The precipitate was removed by filtration and washed with ethyl acetate to give crystals of m.p. 192 C. (decomp.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A stirred mixture of (R)-6,8-difluorochroman-3-ylamine hydrochloride (0.22 g, 1.0 mmol), <strong>[184429-84-3][3-(tert-butyldimethylsilanyloxy)-2-oxopropyl]carbamic acid tert-butyl ester</strong> (0.33 g, 1.1 mmol), potassium thiocyanate (0.11 g, 1.1 mmol) and acetic acid (0.3 mL, 5.0 mmol) in ethyl acetate (3 mL) was refluxed for 2 hours, cooled to room temperature, then washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by the column chromatography over silica gel using ethyl acetate - petroleum ether mixture as eluent. The resulting oil (0.23 g) was dissolved in ethyl acetate (2 ml), whereupon 2M HCl solution in ethyl acetate was added (2 mL, 4 mmol) and the mixture was stirred for 2 hours at room temperature. The precipitate was removed by filtration and washed with ethyl acetate to give crystals of m.p. 192 C (decomp.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A stirred mixture of 6-hydroxythiochroman-3-ylamine hydrochloride (0.22 g, 1.0 mmol), <strong>[184429-84-3][3-(tert-butyldimethylsilanyloxy)-2-oxopropyl]carbamic acid tert-butyl ester</strong> (0.33 g, 1.1 mmol), potassium thiocyanate (0.11 g, 1.1 mmol) and acetic acid (0.3 mL, 5.0 mmol) in ethyl acetate (3 mL) was refluxed for 2 hours, then cooled to room temperature, and washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by column chromatography on silica using ethyl acetate - petroleum ether mixture as eluent. The resulting oil (0.25 g) was dissolved in ethyl acetate (2 ml), whereupon 2M HCl solution in ethyl acetate was added (2 mL, 4 mmol) and the mixture was stirred for 2 hours at room temperature. The precipitate was removed by filtration and washed with ethyl acetate to give crystals, which decomposed without melting. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A stirred mixture of 6-methoxythiochroman-3-ylamine hydrochloride (0.12 g, 0.50 mmol), <strong>[184429-84-3][3-(tert-butyldimethylsilanyloxy)-2-oxopropyl]carbamic acid tert-butyl ester</strong> (0.17 g, 0.55 mmol), potassium thiocyanate (0.055 g, 0.55 mmol), water (0.009 g, 0.50 mmol) and acetic acid (0.2 mL, 3.3 mmol) in ethyl acetate (2 mL) was refluxed for 7 hours, cooled to room temperature, washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by column chromatography on silica using ethyl acetate - petroleum ether mixture as eluent. The resulting oil (0.12 g) was dissolved in ethyl acetate (1 ml), 2M HCl solution in ethyl acetate was added (1 mL, 2 mmol) and the mixture was stirred for 2 hours at room temperature. The precipitate was removed by filtration and washed with ethyl acetate to give crystals which decomposed without melting. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In ethyl acetate; for 2h;Reflux; | A stirred mixture of 6-hydroxythiochroman-3-ylamine hydrochloride (0.22 g, 1.0 mmol), <strong>[184429-84-3][3-(tert-butyldimethylsilanyloxy)-2-oxopropyl]carbamic acid tert-butyl ester</strong> (0.33 g, 1.1 mmol), potassium thiocyanate (0.11 g, 1.1 mmol) and acetic acid (0.3 mL, 5.0 mmol) in ethyl acetate (3 mL) was refluxed for 2 hours, then cooled to room temperature, and washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by column chromatography on silica using ethyl acetate-petroleum ether mixture as eluent. The resulting oil (0.25 g) was dissolved in ethyl acetate (2 ml), whereupon 2M HCl solution in ethyl acetate was added (2 mL, 4 mmol) and the mixture was stirred for 2 hours at room temperature. The precipitate was removed by filtration and washed with ethyl acetate to give crystals, which decomposed without melting. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In water; ethyl acetate; for 7h;Reflux; | A stirred mixture of 6-methoxythiochroman-3-ylamine hydrochloride (0.12 g, 0.50 mmol), <strong>[184429-84-3][3-(tert-butyldimethylsilanyloxy)-2-oxopropyl]carbamic acid tert-butyl ester</strong> (0.17 g, 0.55 mmol), potassium thiocyanate (0.055 g, 0.55 mmol), water (0.009 g, 0.50 mmol) and acetic acid (0.2 mL, 3.3 mmol) in ethyl acetate (2 mL) was refluxed for 7 hours, cooled to room temperature, washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by column chromatography on silica using ethyl acetate-petroleum ether mixture as eluent. The resulting oil (0.12 g) was dissolved in ethyl acetate (1 ml), 2M HCl solution in ethyl acetate was added (1 mL, 2 mmol) and the mixture was stirred for 2 hours at room temperature. The precipitate was removed by filtration and washed with ethyl acetate to give crystals which decomposed without melting. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | (Fluoromethyl)triphenylphosphonium tetrafluoroborate (5.0 g, 13.1 mmol, 1.5 eq) was dissolved in anhydrous water under nitrogen.In THF (50 mL), the mixture was cooled to -20 C, and NaHMDS (1.6 M, 6.5 mL, 10.45 mmol, 1.5 eq) was slowly added dropwise.Add the insulation for 10 minutes.Slowly adding (3-((tert-butyldimethylsilyl)oxy)-2-oxopropyl)carbamic acid tert-butyl ester(2.64 g, 8.7 mmol, 1.0 eq) in THF (5 mL)After the incubation for 1 hour, the temperature was returned to room temperature, and the reaction was completely detected by LC-MS.The reaction was quenched by dropwise addition of water (10 mL), and the mixture was concentrated to viscous liquid.Add water (50 mL) and extract with ether (50 mL) three times.Combine the organic phases, dry and concentrate.The crude product was subjected to silica gel column chromatography (100-200 mesh silica gel,Purified colorless viscous liquid by petroleum ether / ethyl acetate = 0-30%(cis-trans isomer mixture, 4.0 g, 97%). | |
94% | To a vigorously stirring suspension of fluoromethyl(triphenyl)-phosphonium tetrafluoroborate (18.9 g, 49.4 mmol) in dry THF (190 mL) at -20 C under N2 was added sodium bis(trimethylsilyl)amide (1.0 M in THF; 49.4 niL, 49,4 mmol) slowly over 10 min. The resulting deep orange solution was left to stir at this temperature for 15 min. A solution of <strong>[184429-84-3]tert-butyl 3-(tert-butyldimethylsilyloxy)-2-oxopropylcarbamate</strong> (10.0 g, 33.0 mmol) in THF (10 mL) was then added slowly over 10 min. After complete addition, stirring was continued for a further 1 h during which time the reaction was allowed to warm slowly to room temperature. The reaction was quenched by addition of water (5 mL) and the reaction mixture was concentrated in vacuo. The residue was partitioned between water (100 mL) and diethyl ether (100 mL) and the aqueous layer was extracted with further diethyl ether (2 x 100 ml). The combined organics were dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified over silica gel eluting with n-hexane followed by 6 % ethylacetate in n-hexane to give tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-3-fluoroallylcarbamate as a mixture of E/Z double-bond isomers (E/Z = 1:1; 9.9 g, 94%). The isomers were not separated at this stage. | |
76.7% | To a suspension of (fluoromethyl)triphenylphosphonium tetrafluoroborate (32.74 g, 85.68 mmol, BF4) in THF (200 mL) at -78 C under N2 was added NaHMDS (1M, 85.68 mL) over 30 min, the mixture was stirred for lh at -78 C. A solution of compound 12B (13 g, 42.84 mmol) in THF (50 mL) was added slowly. After addition, the mixture was stirred for 20h at -78 C. The reaction mixture was quenched by water (300 mL), concentrated to remove THF, then extracted with TBME (100 mL x 3), the organic layers were washed with brine (100 mL), dried over Na2S04, filtered and concentrated to give a residue. The residue was purified by flash silica gel chromatography (ISCO; 120 g SepaFlash Silica Flash Column, Eluent of 0 ~ 10% Ethyl acetate/Petroleum ether gradient 85 mL/min). Compound 12C (10.5 g, yield: 76.7%) as light yellow oil was obtained. 'H NMR (400MHz, CDCb) d 6.66 - 6.39 (m, 1H), 4.82 (s, 1H), 4.02 (dd, / = 1.2, 4.4 Hz, 2H), 3.82 (d, J = 3.4 Hz, 2H), 1.36 (s, 9H), 0.82 (s, 9H), 0.01 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A stirred mixture of (R)-6,8-difluorochroman-3-ylamine hydrochloride (0.22 g, 1.0 mmol), <strong>[184429-84-3][3-(tert-butyldimethylsilanyloxy)-2-oxopropyl]carbamic acid tert-butyl ester</strong> (0.33 g, 1.1 mmol), potassium thiocyanate (0.11 g, 1.1 mmol) and acetic acid (0.3 mL, 5.0 mmol) in ethyl acetate (3 mL) was refluxed for 2 hours, cooled to room temperature, then washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by the column chromatography over silica gel using ethyl acetate - petroleum ether mixture as eluent. The resulting oil (0.23 g) was dissolved in ethyl acetate (2 ml), whereupon 2M HC1 solution in ethyl acetate was added (2 mL, 4 mmol) and the mixture was stirred for 2 hours at room temperature. The precipitate was removed by filtration and washed with ethyl acetate to give crystals of m.p. 192 oC (decomp.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Triethyl 2-fluoro-2-phosphonoacetate (0.48 g, 2.0 mmol) was dissolved in tetrahydrofuran (5 mL).Cool down to -78 C,Add a solution of n-butyllithium in tetrahydrofuran (0.83 mL, 2.0 mmol, 2.4 mol/L).After stirring for 30 minutes,A solution of tert-butyl 3-(tert-butyldimethylsilyloxy)-2-oxypropylcarbamate 20a (0.30 g, 0.99 mmol) in tetrahydrofuran (1.0 mL)After reacting for 1 hour, the temperature was slowly raised to 0 C for 4.5 hours.The mixture was diluted with aq. EtOAc (EtOAc) (EtOAc)Filtration, concentration under reduced pressure, and the residue was purified by column chromatography [ethyl acetate / petroleum ether (v/v) = 1/20]Get the title compound 20bAnd a mixture of the title compound 20c,It was a pale yellow oil (0.18 g, yield 47%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Triethyl 2-fluoro-2-phosphonoacetate (0.48 g, 2.0 mmol) was dissolved in tetrahydrofuran (5 mL).Cool down to -78 C,Add a solution of n-butyllithium in tetrahydrofuran (0.83 mL, 2.0 mmol, 2.4 mol/L).After stirring for 30 minutes,A solution of tert-butyl 3-(tert-butyldimethylsilyloxy)-2-oxypropylcarbamate 20a (0.30 g, 0.99 mmol) in tetrahydrofuran (1.0 mL)After reacting for 1 hour, the temperature was slowly raised to 0 C for 4.5 hours.The mixture was diluted with aq. EtOAc (EtOAc) (EtOAc)Filtration, concentration under reduced pressure, and the residue was purified by column chromatography [ethyl acetate / petroleum ether (v/v) = 1/20]Get the title compound 20bAnd a mixture of the title compound 20c,It was a pale yellow oil (0.18 g, yield 47%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of (fluoromethyl)triphenylphosphonium bromide (29 g, 77.3 mmol) in THF (300 mL) was cooled to -20 C before the dropwise addition of a 1M NaHMDS solution in THF (206 mL, 206 mmol). The mixture was stirred at -20 C for 30 min before the addition of a solution of tert- butyl (3-((/er/-butyldimethylsilyl)oxy)-2-oxopropyl)carbamate (15.6 g, 51.5 mmol) in THF (100 mL). The reaction was warmed to room temperature and stirred for 2 h. The reaction mixture was poured into water (1000 mL) and extracted with EtOAc (3x500 mL). The combined organics were washed with brine (2x500 mL), dried (Na2S0 ) and concentrated under reduced pressure. Purification by flash chromatography on silica gel (0-2% ethyl acetate in petroleum ether) gave a 4: 1 mixture of E:Z regioisomers of tert- butyl (2-(((/er/-butyldimethylsilyl)oxy)methyl)-3- fluoroallyl)carbamate (22.9 g, 69 %) isolated as a yellow oil. 1H NMR (400 MHz, CDCI3) d 6.61 (d, 0.8H), 6.57 (d, 0.2H), 5.05 (s, 0.2H), 4.90 (s, 0.8H), 4.34-4.09 (m, 2H), 3.90-3.68 (m, 2H), 1.45 (s, 9H), 0.91 (s, 9H), 0.08 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With potassium tert-butylate; In N,N-dimethyl-formamide; at -50 - 18℃; for 1h; | tert-butyl (3,3-difluoro-2-(hydroxymethyl)allyl)carbamate was prepared according to the following procedure. To a stirring solution of tert- butyl (3-((tert-butyldimethylsilyl)oxy)-2- oxopropyl)carbamate (1.0 g, 3.29 mmol) and <strong>[1219454-89-3]2-((difluoromethyl)sulfonyl)pyridine</strong> (0.53 g, 2.75 mmol) in DMF (30 mL) cooled to -50 C was added‘BuOK (0.55 g, 4.95 mmol). The reaction was allowed to warm to 18 C and was stirred for 1 hr. Sat. aq. NH4CI (15 mL) was added followed by 3M HC1 (15 mL). The reaction was stirred for 15 hr at 18 C. The mixture was extracted with EtOAc (3x20 mL), combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by automated FCC to afford tert-butyl (3,3-difluoro-2- (hydroxymethyl)allyl)carbamate (150 mg, 20 %) as a yellow oil. ' H NMR (299 MHz, Chloroform-ri) d 4.88 (s, 1H), 4.15 (s, 2H), 3.85 (dd, J= 6.6, 2.0 Hz, 2H), 1.45 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25.5% | With lithium hexamethyldisilazane; In tetrahydrofuran; N,N-dimethyl-formamide; at -70℃; for 0.5h;Inert atmosphere; | kinder nitrogen condition, 2.4 g of tert-butyl A-[3 -[tert-butyl (dimethyl )silyl]oxy-2- oxo-propyl]carbamate and 1.0 g of 2-(difluoromethylsulfonyl)pyridine were dissolved in 34.5 mL of Af,A-di methyl form amide and then cooled to -70 C. To the reaction mixture, 10.4 mL of a tetrahydrofuran solution of 1.0 M lithium bis(trimethylsilyl)amide was slowly added dropwise. The resulting solution was stirred at -70 C for 30 minutes and then stirred again by slowly increasing the temperature to -10 C. 20 mL of an ammonium chloride solution was added to the reaction mixture, followed by the addition of 20 mL of a 3 N hydrogen chloride solution. The reaction mixture was extracted with ethyl acetate three times. The extracted organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a yellow liquid residue. The residue was purified with silica gel column chromatography (developing solvent: n-hexane/ethyl acetate = 20/1) to give 446.0 mg of the title compound as a yellow liquid (yield: 25.5 %). ^NMR (CDCb, 400 MHz) d 4.98(s, 1H), 4.20(s, 2H), 3.83(s, 2H), 1.42(s, 9H), 0.89(s, 9H), 0.07(s, 6H) |
25.5% | With lithium hexamethyldisilazane; In tetrahydrofuran; N,N-dimethyl-formamide; at -70 - -10℃;Inert atmosphere; | Under nitrogen condition, 2.4 g of tert-butyl l-[3 -[tert-butyl (dimethyl )silyl]oxy- 2-oxo-propyl]carbamate and 1.0 g of 2-(difluoromethylsulfonyl)pyridine were dissolved in 34.5 mL of /'/,/V-dimethylformamide and then cooled to -70 C. To the reaction mixture, 10.4 mL of a tetrahydrofuran solution of 1.0 M lithium bis(trimethylsilyl)amide was slowly added dropwise. The resulting solution was stirred at -70 C for 30 minutes and then stirred again by slowly increasing the temperature to -10 C. 20 mL of an ammonium chloride solution was added to the reaction mixture, followed by the addition of 20 mL of a 3 N hydrogen chloride solution. The reaction mixture was extracted with ethyl acetate three times. The extracted organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a yellow liquid residue. The residue was purified with silica gel column chromatography (developing solvent: n-hexane/ethyl acetate = 20/1) to give 446 mg of the title compound as a yellow liquid (yield: 25.5 %). -NMR (CDCb, 400 MHz) d 4.98(s, 1H), 4.20(s, 2H), 3.83(s, 2H), 1.42(s, 9H), 0.89(s, 9H), 0.07(s, 6H) |
Tags: 184429-84-3 synthesis path| 184429-84-3 SDS| 184429-84-3 COA| 184429-84-3 purity| 184429-84-3 application| 184429-84-3 NMR| 184429-84-3 COA| 184429-84-3 structure
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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.
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