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CAS No. : | 34619-03-9 |
Formula : | C9H18O3 |
M.W : | 174.24 |
SMILES Code : | O=C(OC(C)(C)C)OC(C)(C)C |
MDL No. : | MFCD14560560 |
InChI Key : | ODCCJTMPMUFERV-UHFFFAOYSA-N |
Pubchem ID : | 10219638 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
* 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 |
---|---|---|
88% | Stage #1: With methanesulfonic acid In tetrahydrofuran; water at 34 - 44℃; for 2.75 h; Heating / reflux Stage #2: With lithium aluminium tetrahydride In tetrahydrofuran for 18.5 h; Heating / reflux | The first filtrate of Example 2 containing (-)-(1S, 4R-amino-2-cycopentene-1-methanol was cooled in anice-acetone bath and treated with di-tert-butyl dicarbonate (199.42 g, 0.9265 mol, Aldrich). The mixture was concentrated under vacuum to a volume of 300 mL, and added to the second filtrate of Example 2 that had meanwhile been cooled in an ice-acetone bath. The mixture was allowed to stir and warm to room temperature over the course of 18 hours, during which time gas evolved and a clear solution formed. This solution was combined with the last filtrate of Example 2 which had been evaporated under vacuum to a mixture of oil and solids. The resulting solution was evaporated under vacuum to an oil. The oil was partitioned between ethyl acetate (300 mL) and phosphate buffer (100 mL of 1.5 molar potassium dihydrogen phosphate adjusted to pH 7.0 with 50percent sodium hydlroxide-water). The phases were separated, the aqueous phase was reextracted twice with ethyl acetate (200 mL). The organic phases were dried over sodium sulfate and filtered through silica gel (50 g.). The solvent was removed under vacuum to give an oil (220.78 g), which was taken up in hexanes (300 mL). A minimum amount of ethyl acetate (about 50 mL) was added in order to dissolve the oil, and the solution was set to crystallize over the course of three days. The crystals were filtered off, washed with 20percent ethyl acetate/hexanes, and dried by suction to a constantweight (156.1 g, 0.732 mol, 82.6percent of theory) of the title compound; m.p. 73-73.7° C.; 1 H-NMR (DMSO-d6) 5: 6.72 (d, J=7.9 Hz, 1H, NH), 5.80 and 5.60 (two m, 2H, CHCH), 4.59 (t, J=5.2 Hz, 1H, OH), 4.45 (m, 1H, CHN), 3.35 (m, overlapping H2O, CH2O), 2.60 (m, 1H, CH), 2.30 (m, 1H, 1/2 CH2), 1.40 (s, 9H, C(CH3)3), 1.2 (m, 1H, 1/2CH2); [α]20589-2.78°, [α]20578-2.84°, [α]20546-3.6°, [α]20436-3.39°, [α]20365-0.95° (c=5.07, methanol); Cl-MS (CH4) 214 (M+1); TLC (silica, 10percent methanol-chloroform, iodine visualization), Rf=0.51. Anal. Calcd. for C11H19O13N: C, 61.95; H, 8.98, N, 6.57. Found: C, 61.87; H, 8.96; N, 6.59. An additional 10.14 g of crystalline material was recovered from the mother liquor by crystallization and chromatography, bringing the total yield to 166.24 g (0.780 mol, 87.9percent of theory from the lactam starting material of Example 1). It was also found convenient to prepare the title compound directly from 2-azabicyclo [2.2.1] hept-S-en-3-one, either racemic or the (-) enantiomer, as follows. (-)2-Azabicyclo [2.2.1] hept-S-en-3-one (6.00 g, 55.0 mmol) in anhydroustetrahydrofuran (30 mL) was warmed to 34° C. and stirred while methanesulfonic acid (3.6 mL, 55 mmol) and water (0.99 mL, 55 mmol) were added dropwise over 10 minutes. An exotherm of 10° C. was observed within 5 minutes and a crystalline solid began to precipitate. The mixture was refluxed (oil bath at 74° C.) for 2.5 hours. The mixture was cooled to -10° C. and a solution of lithium aluminum hydride (1.0 M intetrahydrofuran, 100 mL) added. The first 15 mL was added over 10 minutes and an exotherm of 7° C. noted. The remaining 85 mL was added rapidly with no further exotherm noted. The mixture was brought to reflux over 30 minutes and reflux continued for 18hours. The mixture was cooled to 25° C.and sodium fluoride (25.2 g, 0.600 mole) was added and, after stirring for 30 minutes water (5.3 mL) was added dropwise over 10 minutes to the cooled (0° C.) mixture. The mixture was stirred for 30 minutes at 25° C. and di-tert-butyl dicarbonate (12.6 mL, 55.0 mmol) was added. This mixture was stirred for 16 hours, filtered, and the cake triturated with ethyl acetate (2.x.50 mL). The combined filteratewash was washed with water (20 mL), dried (Na2SO4), evaporated, and the residual syrup crystallized from ethyl acetate:hexanes/1:2 (30 mL) to give title compound as white crystals (10.32 g, 88percent), identical in properties to the above-described samp |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.6% | at 20℃; for 18 h; | The first filtrate of Example 2 containing (-)-(1S, 4R-amino-2-cycopentene-1-methanol was cooled in anice-acetone bath and treated with di-tert-butyl dicarbonate (199.42 g, 0.9265 mol, Aldrich). The mixture was concentrated under vacuum to a volume of 300 mL, and added to the second filtrate of Example 2 that had meanwhile been cooled in an ice-acetone bath. The mixture was allowed to stir and warm to room temperature over the course of 18 hours, during which time gas evolved and a clear solution formed. This solution was combined with the last filtrate of Example 2 which had been evaporated under vacuum to a mixture of oil and solids. The resulting solution was evaporated under vacuum to an oil. The oil was partitioned between ethyl acetate (300 mL) and phosphate buffer (100 mL of 1.5 molar potassium dihydrogen phosphate adjusted to pH 7.0 with 50percent sodium hydlroxide-water). The phases were separated, the aqueous phase was reextracted twice with ethyl acetate (200 mL). The organic phases were dried over sodium sulfate and filtered through silica gel (50 g.). The solvent was removed under vacuum to give an oil (220.78 g), which was taken up in hexanes (300 mL). A minimum amount of ethyl acetate (about 50 mL) was added in order to dissolve the oil, and the solution was set to crystallize over the course of three days. The crystals were filtered off, washed with 20percent ethyl acetate/hexanes, and dried by suction to a constantweight (156.1 g, 0.732 mol, 82.6percent of theory) of the title compound; m.p. 73-73.7° C.; 1 H-NMR (DMSO-d6) 5: 6.72 (d, J=7.9 Hz, 1H, NH), 5.80 and 5.60 (two m, 2H, CHCH), 4.59 (t, J=5.2 Hz, 1H, OH), 4.45 (m, 1H, CHN), 3.35 (m, overlapping H2O, CH2O), 2.60 (m, 1H, CH), 2.30 (m, 1H, 1/2 CH2), 1.40 (s, 9H, C(CH3)3), 1.2 (m, 1H, 1/2CH2); [α]20589-2.78°, [α]20578-2.84°, [α]20546-3.6°, [α]20436-3.39°, [α]20365-0.95° (c=5.07, methanol); Cl-MS (CH4) 214 (M+1); TLC (silica, 10percent methanol-chloroform, iodine visualization), Rf=0.51. Anal. Calcd. for C11H19O13N: C, 61.95; H, 8.98, N, 6.57. Found: C, 61.87; H, 8.96; N, 6.59. An additional 10.14 g of crystalline material was recovered from the mother liquor by crystallization and chromatography, bringing the total yield to 166.24 g (0.780 mol, 87.9percent of theory from the lactam starting material of Example 1). It was also found convenient to prepare the title compound directly from 2-azabicyclo [2.2.1] hept-S-en-3-one, either racemic or the (-) enantiomer, as follows. (-)2-Azabicyclo [2.2.1] hept-S-en-3-one (6.00 g, 55.0 mmol) in anhydroustetrahydrofuran (30 mL) was warmed to 34° C. and stirred while methanesulfonic acid (3.6 mL, 55 mmol) and water (0.99 mL, 55 mmol) were added dropwise over 10 minutes. An exotherm of 10° C. was observed within 5 minutes and a crystalline solid began to precipitate. The mixture was refluxed (oil bath at 74° C.) for 2.5 hours. The mixture was cooled to -10° C. and a solution of lithium aluminum hydride (1.0 M intetrahydrofuran, 100 mL) added. The first 15 mL was added over 10 minutes and an exotherm of 7° C. noted. The remaining 85 mL was added rapidly with no further exotherm noted. The mixture was brought to reflux over 30 minutes and reflux continued for 18hours. The mixture was cooled to 25° C.and sodium fluoride (25.2 g, 0.600 mole) was added and, after stirring for 30 minutes water (5.3 mL) was added dropwise over 10 minutes to the cooled (0° C.) mixture. The mixture was stirred for 30 minutes at 25° C. and di-tert-butyl dicarbonate (12.6 mL, 55.0 mmol) was added. This mixture was stirred for 16 hours, filtered, and the cake triturated with ethyl acetate (2.x.50 mL). The combined filteratewash was washed with water (20 mL), dried (Na2SO4), evaporated, and the residual syrup crystallized from ethyl acetate:hexanes/1:2 (30 mL) to give title compound as white crystals (10.32 g, 88percent), identical in properties to the above-described samp |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With sodium hydroxide In 1,4-dioxane; water | A solution of 3-aminocyclohexanecarboxylic acid (1.005 g, 7.02 mmol) in a mixture of a 2N-aqueous sodium hydroxide solution (14 ml, 28 mmol) and 1,4-dioxane (15 ml) was cooled on a water bath, and di-tert-butyl dicarbonate (3.25 ml, 14.1 mmol) was added thereto and stirred overnight. The resulting solution was diluted with water and washed with diethyl ether, and the aqueous layer was adjusted to pH 6 to 7 with 1N-hydrochloric acid and then to pH 2 to 3 with a 5percent-aqueous potassium hydrogensulfate solution. The aqueous layer was extracted three times with ethyl acetate, and the extract solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 3-[(tert-butoxycarbonyl)amino]cyclohexanecarboxylic acid (1.587 g, 93percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; potassium hydrogensulfate; In 1,4-dioxane; | b 3-[N-(tert-butoxycarbonyl)piperidin-4-yl]propanol A solution of 6 g of di(tert-butyl)carbonate in 20 ml of dioxan was introduced into a solution of 3.2 g of 3-(4-piperidinyl)propanol in 50 ml of dioxan containing 25 ml of a 2N aqueous solution of sodium hydroxide, cooled at 0° C. The mixture was allowed to react for 16 hours at room temperature. The solution was then evaporated and the residue was extracted with ethylether. The organic layer was washed with a 10percent solution of KHSO4 and then dried over MgSO4. The solvent was evaporated and the residue was chromatographied on silica gel (eluent: CH3 COOEt/cyclohexane:2/8-1/1:v:v). 3 g of the desired compound in the form of an oil were obtained. RMN (CDCl3, 200 MHz) 4.05 ppm (m, 2H); 3.6 (t, 2H); 2.64 (m,2H); 1.7 a 1.1 (m, 18H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.6% | at 20℃; for 18h; | The first filtrate of Example 2 containing (-)-(1S, 4R-amino-2-cycopentene-1-methanol was cooled in anice-acetone bath and treated with di-tert-butyl dicarbonate (199.42 g, 0.9265 mol, Aldrich). The mixture was concentrated under vacuum to a volume of 300 mL, and added to the second filtrate of Example 2 that had meanwhile been cooled in an ice-acetone bath. The mixture was allowed to stir and warm to room temperature over the course of 18 hours, during which time gas evolved and a clear solution formed. This solution was combined with the last filtrate of Example 2 which had been evaporated under vacuum to a mixture of oil and solids. The resulting solution was evaporated under vacuum to an oil. The oil was partitioned between ethyl acetate (300 mL) and phosphate buffer (100 mL of 1.5 molar potassium dihydrogen phosphate adjusted to pH 7.0 with 50% sodium hydlroxide-water). The phases were separated, the aqueous phase was reextracted twice with ethyl acetate (200 mL). The organic phases were dried over sodium sulfate and filtered through silica gel (50 g.). The solvent was removed under vacuum to give an oil (220.78 g), which was taken up in hexanes (300 mL). A minimum amount of ethyl acetate (about 50 mL) was added in order to dissolve the oil, and the solution was set to crystallize over the course of three days. The crystals were filtered off, washed with 20% ethyl acetate/hexanes, and dried by suction to a constantweight (156.1 g, 0.732 mol, 82.6% of theory) of the title compound; m.p. 73-73.7 C.; 1 H-NMR (DMSO-d6) 5: 6.72 (d, J=7.9 Hz, 1H, NH), 5.80 and 5.60 (two m, 2H, CHCH), 4.59 (t, J=5.2 Hz, 1H, OH), 4.45 (m, 1H, CHN), 3.35 (m, overlapping H2O, CH2O), 2.60 (m, 1H, CH), 2.30 (m, 1H, ½ CH2), 1.40 (s, 9H, C(CH3)3), 1.2 (m, 1H, ½CH2); [alpha]20589-2.78, [alpha]20578-2.84, [alpha]20546-3.6, [alpha]20436-3.39, [alpha]20365-0.95 (c=5.07, methanol); Cl-MS (CH4) 214 (M+1); TLC (silica, 10% methanol-chloroform, iodine visualization), Rf=0.51. Anal. Calcd. for C11H19O13N: C, 61.95; H, 8.98, N, 6.57. Found: C, 61.87; H, 8.96; N, 6.59. An additional 10.14 g of crystalline material was recovered from the mother liquor by crystallization and chromatography, bringing the total yield to 166.24 g (0.780 mol, 87.9% of theory from the lactam starting material of Example 1). It was also found convenient to prepare the title compound directly from 2-azabicyclo [2.2.1] hept-S-en-3-one, either racemic or the (-) enantiomer, as follows. (-)2-Azabicyclo [2.2.1] hept-S-en-3-one (6.00 g, 55.0 mmol) in anhydroustetrahydrofuran (30 mL) was warmed to 34 C. and stirred while methanesulfonic acid (3.6 mL, 55 mmol) and water (0.99 mL, 55 mmol) were added dropwise over 10 minutes. An exotherm of 10 C. was observed within 5 minutes and a crystalline solid began to precipitate. The mixture was refluxed (oil bath at 74 C.) for 2.5 hours. The mixture was cooled to -10 C. and a solution of lithium aluminum hydride (1.0 M intetrahydrofuran, 100 mL) added. The first 15 mL was added over 10 minutes and an exotherm of 7 C. noted. The remaining 85 mL was added rapidly with no further exotherm noted. The mixture was brought to reflux over 30 minutes and reflux continued for 18hours. The mixture was cooled to 25 C.and sodium fluoride (25.2 g, 0.600 mole) was added and, after stirring for 30 minutes water (5.3 mL) was added dropwise over 10 minutes to the cooled (0 C.) mixture. The mixture was stirred for 30 minutes at 25 C. and di-tert-butyl dicarbonate (12.6 mL, 55.0 mmol) was added. This mixture was stirred for 16 hours, filtered, and the cake triturated with ethyl acetate (2×50 mL). The combined filteratewash was washed with water (20 mL), dried (Na2SO4), evaporated, and the residual syrup crystallized from ethyl acetate:hexanes/1:2 (30 mL) to give title compound as white crystals (10.32 g, 88%), identical in properties to the above-described samp |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In dichloromethane; at 20℃; for 48h; | Di-tert-butyl dicarbonate (21.8 g) was added to a mixture of intermediate 1 (17 g) in CH2Cl2 (500 ml) and the mixture was stirred at RT for 48 hours. The mixture was evaporated, the residue was taken up in water and toluene and the organic layer was separated. The aqueous layer was extracted again with toluene. The combined organic layers were dried, filtered and evaporated, yielding 38 g (100%) of (+/-)-1,1-dimethylethyl 4-oxo-2-(phenylmethyl)-1-piperidinecarboxylate (intermediate 6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 14h; | To a mixture of H-allo-THr-OH (5.0 g, 41.98 mmol) and DIEA (10.9 g, 83.96 mmol) in DCM (150 mL) was added di-tert-butyl dicarbonate (13.7 g, 62.97 mmol). After stirring at rt for 14h, the reaction mixture was washedwith3x100 mL DCM. The combined organic layer was dried over MgS04 and conentrated. LC/MS indicated most product stayed in theH20 layer. Thus the water layer was concentrated. The product was purified by a flash column chromatography(Si02, 90: 10 DCM: MeOH) to give Boc-allo-THr-OH ; LC-MS (retention time: 0.727 min. ),MS m/z 242 (MNa+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium hydride; In tetrahydrofuran; mineral oil; for 22h; | Add DI-TERT-BUTYL dicarbonate (1.4 g. 6.4 mmol) and sodium hydride (0.15 g, 60% dispersion in mineral oil, 3.8 mmol) to a solution of 4-bromoindole (0.4 mL, 3.2 mmol) in THF (11 mL) at 0 C. Stir the reaction for 22 h, quench with saturated aqueous ammonium chloride, and extract with methylene chloride. Dry the combined organic extracts with sodium sulfate, filter, and concentrate in vacuo. Purify by flash column chromatography, utilizing the appropriate mixture of hexanes and methylene chloride, to provide 0.85 g (90%) of the titled compound as a clear, colorless OIL.'H NMR (CDC13) 8 8. 10 (d, J = 8 HZ, 1H), 7.63 (d, J = 4 Hz, 1H), 7. 38 (d, J = 8 HZ, 1H), 7.16 (t, J = 8 Hz, 1H), 6.64 (d, J = 4 Hz, 1H), 1.67 (s, 9H). TLC (SI02) : Rf 0. 3 (9: 1 hexanes/methylene chloride). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In 1,4-dioxane; | A. N-boc-S-trityl-cysteine, dicyclohexylammonium salt (XX) To a solution of S-trityl cysteine (see Hiskey and Adams, J. Org. Chem., 30:1340, (1965)) (36.3 g, 0.10 mol) in dioxane (200 ml) and 1M aqueous NaOH (100 ml, 0.10 mol) was added di-t-butyl carbonate (25.36 g, 0.12 mol). The resulting opaque solution became warm and effervesced and the pH fell from 12 to 8 over one hour. After stirring for 90 min, 50percent aqueous citric acid (40 ml) was added and the resulting mixture (pH 4) was extracted with ether. The ether was washed with water, then saturated brine, dried (MgSO4), filtered and evaporated to give N-BOC-S-(triphenylmethyl)-cysteine as an oil. Half of this material was dissolved in ether (200 ml) and treated with dicyclohexylamine (10 ml, 50 mmol) to give compound (XX) as a white precipitate which was filtered off, washed with ether and dried (25.1 g, 78percent), mp 205°-207°. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sodium tetrahydroborate;nickel(II) chloride hexahydrate; In methanol; at 0 - 20℃; for 2h; | To an ice cooled solution of the title compound from Step A above (5.6 g), di-tert-butyl dicarbonate (14.06 g) and NiCl2-OH2O (1.53 g) in MeOH, NaBH4 (8.51 g) was added in portions. The mixture was vigorously stirred for Ih at O0C and Ih at room temperature. After the addition of diethylenetriamine (3.5 mL) the mixture was concentrated, diluted with EtOAc, washed subsequently with IN HCl, saturated aqueous NaHCO3 and saturated aqueous NaCl, dried (MgSO4), concentrated to afford the title compound as an off-white solid (7.91 g, 88%). [M+Na]+ = 397. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | The first filtrate of Example 2 containing (-)-(1S, 4R-amino-2-cycopentene-1-methanol was cooled in anice-acetone bath and treated with di-tert-butyl dicarbonate (199.42 g, 0.9265 mol, Aldrich). The mixture was concentrated under vacuum to a volume of 300 mL, and added to the second filtrate of Example 2 that had meanwhile been cooled in an ice-acetone bath. The mixture was allowed to stir and warm to room temperature over the course of 18 hours, during which time gas evolved and a clear solution formed. This solution was combined with the last filtrate of Example 2 which had been evaporated under vacuum to a mixture of oil and solids. The resulting solution was evaporated under vacuum to an oil. The oil was partitioned between ethyl acetate (300 mL) and phosphate buffer (100 mL of 1.5 molar potassium dihydrogen phosphate adjusted to pH 7.0 with 50% sodium hydlroxide-water). The phases were separated, the aqueous phase was reextracted twice with ethyl acetate (200 mL). The organic phases were dried over sodium sulfate and filtered through silica gel (50 g.). The solvent was removed under vacuum to give an oil (220.78 g), which was taken up in hexanes (300 mL). A minimum amount of ethyl acetate (about 50 mL) was added in order to dissolve the oil, and the solution was set to crystallize over the course of three days. The crystals were filtered off, washed with 20% ethyl acetate/hexanes, and dried by suction to a constantweight (156.1 g, 0.732 mol, 82.6% of theory) of the title compound; m.p. 73-73.7 C.; 1 H-NMR (DMSO-d6) 5: 6.72 (d, J=7.9 Hz, 1H, NH), 5.80 and 5.60 (two m, 2H, CHCH), 4.59 (t, J=5.2 Hz, 1H, OH), 4.45 (m, 1H, CHN), 3.35 (m, overlapping H2O, CH2O), 2.60 (m, 1H, CH), 2.30 (m, 1H, ½ CH2), 1.40 (s, 9H, C(CH3)3), 1.2 (m, 1H, ½CH2); [alpha]20589-2.78, [alpha]20578-2.84, [alpha]20546-3.6, [alpha]20436-3.39, [alpha]20365-0.95 (c=5.07, methanol); Cl-MS (CH4) 214 (M+1); TLC (silica, 10% methanol-chloroform, iodine visualization), Rf=0.51. Anal. Calcd. for C11H19O13N: C, 61.95; H, 8.98, N, 6.57. Found: C, 61.87; H, 8.96; N, 6.59. An additional 10.14 g of crystalline material was recovered from the mother liquor by crystallization and chromatography, bringing the total yield to 166.24 g (0.780 mol, 87.9% of theory from the lactam starting material of Example 1). It was also found convenient to prepare the title compound directly from 2-azabicyclo [2.2.1] hept-S-en-3-one, either racemic or the (-) enantiomer, as follows. (-)2-Azabicyclo [2.2.1] hept-S-en-3-one (6.00 g, 55.0 mmol) in anhydroustetrahydrofuran (30 mL) was warmed to 34 C. and stirred while methanesulfonic acid (3.6 mL, 55 mmol) and water (0.99 mL, 55 mmol) were added dropwise over 10 minutes. An exotherm of 10 C. was observed within 5 minutes and a crystalline solid began to precipitate. The mixture was refluxed (oil bath at 74 C.) for 2.5 hours. The mixture was cooled to -10 C. and a solution of lithium aluminum hydride (1.0 M intetrahydrofuran, 100 mL) added. The first 15 mL was added over 10 minutes and an exotherm of 7 C. noted. The remaining 85 mL was added rapidly with no further exotherm noted. The mixture was brought to reflux over 30 minutes and reflux continued for 18hours. The mixture was cooled to 25 C.and sodium fluoride (25.2 g, 0.600 mole) was added and, after stirring for 30 minutes water (5.3 mL) was added dropwise over 10 minutes to the cooled (0 C.) mixture. The mixture was stirred for 30 minutes at 25 C. and di-tert-butyl dicarbonate (12.6 mL, 55.0 mmol) was added. This mixture was stirred for 16 hours, filtered, and the cake triturated with ethyl acetate (2×50 mL). The combined filteratewash was washed with water (20 mL), dried (Na2SO4), evaporated, and the residual syrup crystallized from ethyl acetate:hexanes/1:2 (30 mL) to give title compound as white crystals (10.32 g, 88%), identical in properties to the above-described samp |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 1.75h; | Preparation J(2-Hydroxy-1-hvdroxymethyl-ethyl)-carbamic acid tert-butyl esterO H ^OH <n="23"/>2-Amino-1 ,3-propanediol (5.Og, 54.9mmol) was dissolved in dry THF (175ml) and triethylamine (7.7ml) added. The solution was cooled in an ice-bath and di-te/f- butylcarbonate (11.98g, 54.9mmol) added in portions over 15mins. The solution was allowed to warm to ambient temperature and stirred for 90mins. The solvent was evaporated and water (250ml) added and the product extracted into ethyl acetate (4 x 125ml). The combined organics were washed with brine, dried over magnesium sulphate, filtered and evaporated. The product was isolated by recrystallization from hot ethyl acetate-petrol (1 :3) to give shiny flakes 5.18g (49% yield).The structure was confirmed by 1H NMR (300MHz , CDCI3): 1.44 (s, 9H), 3.08- 3.17 (m, 1 H), 3.61 - 3.84 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sodium hydroxide; In 1,4-dioxane; water; at 20℃; for 20h;Cooling with ice; Inert atmosphere; | To a suspension of (R)-2-amino-3-mercapto-3-methylbutanoic acid (8.0 g, 53.6 mmol) in 1,4-dioxane (90 mL) was added a solution of NaOH (4.72 g, 1 18 mmol) in water (45 mL). The reaction mixture was then cooled with an ice bath, and at this point di-?-butyldicarbonate (14.04 g, 64.3 mmol) was added dropwise. The reaction mixture was then stirred at rt for 20 h and then extracted with EtOAc. The aqueous layer was acidified with 2N HC1 solution (pH = 1). The resulting aqueous layer was extracted with EtOAc (3x). The organic layer was separated and dried over MgS04. The filtrate was concentrated in vacuo and dried under vacuum to give the title compound as a white solid (1 1.8 g, 88%). XH NMR (DMSO-d6) delta 6.90 (d, J= 9.2 Hz, 1H), 4.07 (d, J= 9.2 Hz, 1H), 3.57 (s, 1H), 3.00 (br. s, 1H), 1.40 (s, 15H); MS(ESI+) m/z 194.1 (M-56) (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With sodium borodeuteride; nickel(II) chloride * 6 D2O; In d(4)-methanol; at 0 - 20℃;Inert atmosphere; | 3-Oxo-3,4-dihydro-2H-benzo[l,4]oxazine-6-carbonitrile (10) (1.0 mmole) is added to a 50 ml round bottom flask containing a stir bar. To the flask is then added NiCl2*6D20 (0.1 mmoles) (NiCl2*6D20 was synthesized following the method outlined in Example 2). To the 50 ml flask was then added ditertbutlycarbonate (1.8 mmole) and mixture partially dissolved in 3 ml of anhydrous CD3OD (obtained from Acros Organics) and mixture cooled to 0 C under nitrogen atmosphere. To the suspension was slowly added in portions a total of 75 milligrams of NaBD4 (commercially obtained from Alfa Aesar) making sure to keep the temperature ~0C. After addition was complete the reaction was stirred under nitrogen atmosphere at 0C for 1 hour and then at room temperature for 24 hours. The volatile components of the reaction mixture were then removed under reduced pressure to give a residue which was taken up in 150 ml of ethylacetate and organic layer washed with 10% citric acid and then saturated sodium bicarbonate. The organic layer was separated and dried over anhydrous magnesium sulphate, filtered and the volatile components removed under reduced pressure to give a solid which was purified by column chromatography (Si02, methylene chloride: methanol 90:10) to give 0.16 grams (55% yield) of [Dideutero-(3-oxo-3,4-dihydro-2H-benzo[l,4]oxazin-6-yl)-methyl]-carbarnic acid tert-butyl ester (11). LC-MS (M-H) 279. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.6% | With sodium carbonate; In 1,4-dioxane; water; at 10 - 20℃; | B, compound 2 (233g, 1.23mol) and sodium carbonate (195g, 1.84mol) is dissolved in dioxane and water mixed solution (1/1,1L). Control of reaction temperature on 10-20C, the batch is added slowly di-tert-butyl dicarbonate (281g, 1.29mol). Reaction control in room temperature to continue the reaction 10-20 hours. TLC (petroleum ether/ethyl acetate = 2/1 volume ratio) display reaction is ended. Reaction solution is distilled under reduced pressure take out the dioxane. Residues via ethyl acetate (400mLx3) extraction. Combining the organic phase, dried by sodium sulfate, filtered and concentrated by reduced pressure distillation yellow solid compound 3 (301g), the yield is 96.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.5% | With sodium carbonate; In water; at 25℃;Green chemistry; | Sequentially put 103g of R-3-aminobutyric acid,105g sodium carbonate,218g di-tert-butyl carbonate,Add to the reaction flask containing 500 mL of water,React at 25 C for 2-6 hours,After the reaction is completed, adjust the pH to 3-4 with 2N hydrochloric acid.The product was extracted twice with 500 mL of ethyl acetate.Spin dry,That is, N-Boc-(R)-3-aminobutyric acid (I),The white solid was 190 g, the yield was 93.5%, and the content was 98% (HPLC method). |
Tags: 34619-03-9 synthesis path| 34619-03-9 SDS| 34619-03-9 COA| 34619-03-9 purity| 34619-03-9 application| 34619-03-9 NMR| 34619-03-9 COA| 34619-03-9 structure
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