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CAS No. : | 79069-15-1 | MDL No. : | MFCD00235945 |
Formula : | C15H23NO4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | MSIDLARYVJJEQY-ZDUSSCGKSA-N |
M.W : | 281.35 | Pubchem ID : | 14427183 |
Synonyms : |
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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 |
---|---|---|
(25)-3-(benzyloxy)-2-[(ter?-butoxycarbonyl)amino]propanoic acid (7.2 g, 24.4 mmole) was dissolved in ethylene glycol dimethyl ether (50 mL). N- Methylmorpholine (2.7 ml, 24.4 mmole) was added, and the resulting clear solution was cooled to -20C. Isobutyl chloroformate (3.19 ml, 24.4 mmole) was added dropwise to cause N-methylmorpholine HCl salt precipitation. Stirring was continued for 15 min and the supernatant was then transferred via a filter-tipped funnel into a rapidly stirred solution of NaBH4 (2.93 g, 73.2 mmole) in ice water and washed with dry DME. After the mixture was stirred for 30 min, it was extracted with EtOAc and washed with H20. The organic layers were combined, dried over Na2S04, and concentrated in vacuo. Purification by chromatography (silica, 4/1 : Hexane/EtOAc, Rf= 0.2) afforded tert-butyl N-[(lR)-2-(benzyloxy)-l- (hydroxymethyl)ethyl]carbamate as a white solid (6.3 g, 92 %). | ||
With borane-THF; In tetrahydrofuran; at 0 - 23℃; | To solution of (L)-N-Boc Ser(OBn)-OH 28 (1 g, 3.38 mmol) in anhydrous THF (6 mL) was added 1 M Borane-THF complex (7.5 mL, 7.5 mmol) at 0 C. After stirring at 0 C for 1 h, the reaction mixture was slowly warmed to 23 C and stirred for 3 h. The reaction mixture was cooled to 0 C, quenched by MeOH, concentrated, diluted with MeOH, and concentrated again. The concentrated oil was then subjected to flash column chromatography (EtOAc/ hexane) on silica gel to afford the alcohol 29 (0.87 g, 91%) as an oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | tert-Butyl N-[(lR)-2- (benzyloxy)-l-(hydroxymethyl)ethyl]carbamate (1.2 g, 4.3 mmole) was dissolved in CH2C12 (40 mL). Dess-Martin periodinane (2.4 g, 5.5 mmole) was added. The solution was stirred for 2 h at room temperature and then quenched with Na2S2(? and saturated bicarbonate solution. After extracting with CH2C12, the organic layer was dried over MgS04, filtered, and concentrated by rotary evaporation. Purification by chromatography (silica, 4/1 : Hexane /EtOAc, R{= 0.4) afforded (S)-tert-butyl l-(benzyloxy)-3-oxopropan-2-ylcarbamate as a white solid (1.1 g, 96%). | |
With sodium hydrogencarbonate; Dess-Martin periodane; In dichloromethane; at 0℃; for 1h; | General procedure: The primary alcohol (890 mg, 1.98 mmol) was dissolved in 30 mL of anhydrous dichloromethane and the solution was cooled to 0 C. After adding 166 mg of sodium carbonate, Dess-Martin Periodinane (0.92 g, 2.18 mmol) was added and the mixture stirred for 1 h at 0 C. As soon as the TLC showed full conversion of the starting material, the reaction was quenched with saturated NaHCO3 solution and 10% sodium thiosulfate solution. The organic layer was then w ashed with brine, dried over sodium sulfate, concentrated in vacuo at low temperature. The crude aldehyde 11a was subjected to the next reaction without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 0℃; for 3h; | Step 2: t-butyl (1S)-2-(benzyloxy)-1-[(3-methylphenoxy)methyl]ethylcarbamate; To t-butyl (1R)-2-(benzyloxy)-1-(hydroxymethyl)ethylcarbamate (3.23 g) obtained in Step 1 were added dichloromethane (40 ml), methanesulfonyl chloride (1.07 ml) and triethylamine (3.20 ml), and the mixture was stirred at 0C for 3 hrs. The reaction mixture was diluted with dichloromethane and, after washing with water, the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated to give a crude product. To this crude product were added dimethylformamide (30 ml) and lithium chloride (2.4 g), and the mixture was stirred overnight at 40C. The solvent was evaporated, and the residue was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated to give a crude product. To this crude product were added dimethylformamide (20 ml), potassium carbonate (2.4 g) and m-cresol (1.47 ml), and the mixture was stirred overnight at 90C. The mixture was diluted with ethyl acetate and, after washing with water, the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained crude product was purified by silica gel chromatography (ethyl acetate-hexane) to give t-butyl (1S)-2-(benzyloxy)-1-[(3-methylphenoxy)methyl]ethylcarbamate (1.5 g). | |
With dmap; triethylamine; In dichloromethane; at 0℃; for 1h; | To a solution of Boc-O-benzyl-serinol (800 mg, 2.84 mmol) in dichloromethane(20 niL) and triethylamine (0.44 niL, 3.13 mmol) at 00C was added methanesulfonyl chloride(0.22 mL, 2.84 mmol) and N'N'-Dimethylaminopyridine (10 mg, 0.08 mmol). The reaction mixture was stirred at 0 0C for Ih and was quenched with 5 drops of water at 0 0C. The organic layer was washed with 2 mL of water, 2 mL of saturated sodium bicarbonate, and then dried over magnesium sulfate. Concentration under reduced pressure resulted in the title compound that was taken to the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8.47 g | With sodium tetrahydroborate; In water; at 0℃; for 0.5h; | To a stirred solution of 28 (9.28 g, 31.7 mmol) and N-methyl morpholine (3.7 mL, 33.7 mmol) in DME (70 mL) was added isobutyl chloroformate (4.3 mL, 33.3 mmol) at -20 C under argon atmosphere. After being stirred for 30 min at 0 C, the reaction mixture was filtered to remove the resulting precipitates. To a cooled suspension of sodium borohydride (2.5 g, 66.5 mmol) in water (30 mL) was added the filtrate at 0 C. Stirring was continued for additional 30 min at the same temperature. The reaction mixture was diluted with EtOAc, washed with hydrochloric acid, water, brine, and dried over Na2SO4. The organic layer was removed by evaporation to give an alcohol 29 as a colorless oil (8.47 g, 96%). 1H NMR (300 MHz, CDCl3): delta 1.43 (s, 9H), 3.60-3.83 (m, 6H), 4.54 (s, 2H), 5.17 (br s, 1H), 7.40-7.28 (m, 5H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate; In water; toluene; at 0 - 20℃; for 2.5h; | A 50% sodium hydroxide solution (350 ML) was added to a toluene (350 ML) solution containing boc-O-benzyl-L-serinol (89.5 g, CAS#120349-75-9). Under ice-cooling, tetrabutylammonium hydrogen sulfate (27 g) was added, and t-butyl bromoacetate ester (141 mL) was added dropwise at 15 C. or lower. After stirring for two hours at the same temperature, the temperature was raised to room temperature, and stirring was continued for 30 minutes. The resultant was diluted in ice cold water (350 ML) and toluene (350 ML). Water (300 ML) and toluene (300 ML) were further added, and the organic layer was partitioned. After the organic layer was washed with brine, it was dried over anhydrous magnesium sulfate. After removing the solvent under a vacuum, the partial purification product (136.8 g) containing the title compound was obtained. The physical property values are as follows. ESI-MS; m/z 418 [M++Na]. 1H-NMR (CDCl3) delta (ppm): 1.43 (s,9H), 1.47 (s, 9H), 3.54-3.69 (m, 4H), 3.90-3.95 (m, 1H), 3.95 (d, J=3.6 Hz, 2H), 4.53 (s, 2H), 7.24-7.32 (m, 5H). |
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