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CAS No. : | 603130-12-7 | MDL No. : | MFCD27987051 |
Formula : | C11H21NO4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | LKBZAGUOZDYGKG-BDAKNGLRSA-N |
M.W : | 231.29 | Pubchem ID : | 10988099 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P264-P280-P302+P352-P305+P351+P338-P332+P313-P337+P313-P362 | UN#: | |
Hazard Statements: | H315-H319 | Packing Group: | |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; Aliquat 336; sodium hydrogencarbonate; potassium bromide In Isopropyl acetate at 0 - 10℃; for 1.5 h; Stage #2: at 5 - 10℃; for 1.5 h; |
A reactor was charged with tert-butyl ((3R, 6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3- yl)carbamate (1700 g; 1 eq.; prepared as described in Kriek et al, Eur. J. Org. Chem. (2003), 13, 2418-2427), NaHC03 (1241 g, 2 eq.), KBr (87 g, 0.1 eq.), TEMPO (17.6 g, 0.015 eq.), Aliquat 336 (17 mL, 0.005 eq.) and iPrOAc (17 L). The suspension was cooled to 0 °C and 10 percent NaOCl solution (10.2 L, 2.33 eq.) was added keeping the internal temperature below 5°C. The suspension was stirred at 10°C for 90 min. No starting material could be detected by TLC (visual control by ninhydrin stain). A 40percent NaHS03 solution (1.5 L) was added at 12°C. 25percent HC1 (2.5 L) was then added at 15°C. The mixture was heated to 20°C. The aq. layer was separated and extracted with iPrOAc (8.5 L). The combined org. layers were washed with water (15 L). The org. layer was concentrated at a jacket temperature of 100 °C and reduced pressure. 18 L solvent were removed, the residue was cooled to 65°C and Hept (14 L) was added. The resulting suspension was cooled to -6 °C and filtered. The product was dried on a 20 L rotary evaporator to yield the title compound as a white solid (1406 g; 78percent> yield).1H-NMR (d6-DMSO): δ = 12.64 (m, 1H), 6.85 (m, 1H), 3.84 (m, 1H), 3.76 (m, 1H), 3.32 (m, 1H), 3.01 (t, J = 10.5 Hz, 1H), 1.92 (m, 2H), 1.53 (m, 2H), 1.39 (s, 9H).GC-MS: tR = 3.49 min; [M+l]+ = 246 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | A reactor was charged with tert-butyl ((3R, 6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3- yl)carbamate (1700 g; 1 eq.; prepared as described in Kriek et al, Eur. J. Org. Chem. (2003), 13, 2418-2427), NaHC03 (1241 g, 2 eq.), KBr (87 g, 0.1 eq.), TEMPO (17.6 g, 0.015 eq.), Aliquat 336 (17 mL, 0.005 eq.) and iPrOAc (17 L). The suspension was cooled to 0 C and 10 % NaOCl solution (10.2 L, 2.33 eq.) was added keeping the internal temperature below 5C. The suspension was stirred at 10C for 90 min. No starting material could be detected by TLC (visual control by ninhydrin stain). A 40% NaHS03 solution (1.5 L) was added at 12C. 25% HC1 (2.5 L) was then added at 15C. The mixture was heated to 20C. The aq. layer was separated and extracted with iPrOAc (8.5 L). The combined org. layers were washed with water (15 L). The org. layer was concentrated at a jacket temperature of 100 C and reduced pressure. 18 L solvent were removed, the residue was cooled to 65C and Hept (14 L) was added. The resulting suspension was cooled to -6 C and filtered. The product was dried on a 20 L rotary evaporator to yield the title compound as a white solid (1406 g; 78%> yield).1H-NMR (d6-DMSO): delta = 12.64 (m, 1H), 6.85 (m, 1H), 3.84 (m, 1H), 3.76 (m, 1H), 3.32 (m, 1H), 3.01 (t, J = 10.5 Hz, 1H), 1.92 (m, 2H), 1.53 (m, 2H), 1.39 (s, 9H).GC-MS: tR = 3.49 min; [M+l]+ = 246 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With hydrogen In methanol for 16h; | |
Multi-step reaction with 2 steps 1: water; acetic acid / tetrahydrofuran / 5 h / 70 °C 2: hydrogen / platinum(IV) oxide / ethyl acetate / 3 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 8.3 g / pyridine / 0 °C 2: 76 percent / DBU / CH2Cl2 / 1 h / 0 °C 3: 89 percent / K2CO3 / 1,2-dichloro-benzene / 5 h / 180 °C 4: KOH / propan-2-ol / 72 h 5: 1.5 g / CH2Cl2 6: 75 percent / H2 / Pd/C / methanol / 16 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: tBuOK / methanol / 2 h 2: 8.3 g / pyridine / 0 °C 3: 76 percent / DBU / CH2Cl2 / 1 h / 0 °C 4: 89 percent / K2CO3 / 1,2-dichloro-benzene / 5 h / 180 °C 5: KOH / propan-2-ol / 72 h 6: 1.5 g / CH2Cl2 7: 75 percent / H2 / Pd/C / methanol / 16 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 76 percent / DBU / CH2Cl2 / 1 h / 0 °C 2: 89 percent / K2CO3 / 1,2-dichloro-benzene / 5 h / 180 °C 3: KOH / propan-2-ol / 72 h 4: 1.5 g / CH2Cl2 5: 75 percent / H2 / Pd/C / methanol / 16 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 89 percent / K2CO3 / 1,2-dichloro-benzene / 5 h / 180 °C 2: KOH / propan-2-ol / 72 h 3: 1.5 g / CH2Cl2 4: 75 percent / H2 / Pd/C / methanol / 16 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: KOH / propan-2-ol / 72 h 2: 1.5 g / CH2Cl2 3: 75 percent / H2 / Pd/C / methanol / 16 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 96 percent / BF3*Et2O; triethylsilane / CH2Cl2 / 1 h / 0 °C 2: tBuOK / methanol / 2 h 3: 8.3 g / pyridine / 0 °C 4: 76 percent / DBU / CH2Cl2 / 1 h / 0 °C 5: 89 percent / K2CO3 / 1,2-dichloro-benzene / 5 h / 180 °C 6: KOH / propan-2-ol / 72 h 7: 1.5 g / CH2Cl2 8: 75 percent / H2 / Pd/C / methanol / 16 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.5 g / CH2Cl2 2: 75 percent / H2 / Pd/C / methanol / 16 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 71 percent / NaIO4 / RuCl3*xH2O / CH2Cl2; acetonitrile; H2O / 3 h / 0 °C 2: TFA / CH2Cl2 / 1 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 71 percent / NaIO4 / RuCl3*xH2O / CH2Cl2; acetonitrile; H2O / 3 h / 0 °C 2: TFA / CH2Cl2 / 1 h 3: 0.77 g / NaHCO3 / dioxane; H2O / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; | 13 To a solution of 3-chloro-6-methoxyquinolin-4-ol (WO 2004058144) (250 mg, 1.19 mmol), tert-butyl [(3R,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]carbamate(Intermediate 5, 276 mg, 1.19 mmol) and triphenylphosphine (375 mg, 1.42 mmol) in dry TΗF (5 mL) was added diisopropylazodicarboxylate (0.258 niL, 1.31 mmol). The resulting mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue was chromatographed on silica gel with hexanes/ ethyl acetate (3 : 1 to 2: 1) and then with dichloromethane/ ethyl acetate (15:1 to 5:1) gave 159 mg (32 % yield) of the product as a colorless solid, mp 173 °C.1H-NMR (DMSO-de) δ: 1.37 (s, 9H); 1.35-1.50 (m, 2H); 1.72 (m, IH); 1.91 (m, IH); 3.03 (dd, IH); 3.31 (m, IH); 3.63 (m, IH); 3.85 (m, IH); 3.91 (s, 3H); 4.16 (dd, IH); 4.26 (dd, IH); 6.80 (d, IH); 7.43 (dd, IH); 7.58 (d, IH); 7.93 (d, IH); 8.68 (s, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With oxalyl dichloride; triethylamine In dichloromethane; dimethyl sulfoxide at -72℃; for 1h; Inert atmosphere; | 22.1 Step 1: Synthesis of compound 22-1 Add oxalyl chloride (110mg, 0.866mmol) and dichloromethane (2mL) to the reaction flask, lower the temperature to -72°C, replace with nitrogen, slowly drop DMSO (101mg, 1.30mmol) into the reaction flask, keep the temperature and stir for 30min , Compound 10-1 (100mg, 0.433mmol) was dissolved in dichloromethane (0.5mL) and slowly dripped, after dripping, keep stirring at this temperature for 30min, triethylamine (220mg, 2.17mmol) was slowly added, after the addition, the The reaction mixture was stirred at -72°C for 0.5 hours. TLC showed that the reaction was complete. Water was added to the reaction system, extracted with dichloromethane three times, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 90 mg of product 22-1. Yield: 91%. The product was used directly in the next step without purification. |
90% | With sulfur trioxide pyridine complex; N-ethyl-N,N-diisopropylamine In dichloromethane; dimethyl sulfoxide at -10 - 0℃; | A.i To a solution of (Ji?,6^5)-(6-hydroxymethyl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester (37.5 g, 162.13 mmol) in DCM (31O mL) cooled to -100C was added DIPEA (84.75 mL, 495.06 mmol). Then a solution of Pyr.SO3 complex (50%, 69.47 g, 218.25 mmol) in DMSO (225 mL) was slowly added. The reaction mixture was stirred for 2 h at 00C .The reaction mixture was partitioned between water (15O mL) and DCM (220 mL). The two layers were separated and the aq. layer was extracted twice with DCM (2 x 150 mL). The combined org. layers were dried over Na2SO4, filtered and concentrated to dryness. The residue was co-evaporated 3 times with toluene and purified over a short pad of silica gel (EA-Hept. 2-1) to afford the title aldehyde as a white solid (33.58 g, 90% yield).MS (ESI, mix): 230.0 [M+H+] for CHHI9NO4. |
90% | With sulfur trioxide pyridine complex; N-ethyl-N,N-diisopropylamine In dichloromethane; dimethyl sulfoxide at -10 - 0℃; | A.i A.i. (3R,6S)-(6-formyl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester To a solution of (3R,6S)-(6-hydroxymethyl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester (37.5 g, 162.13 mmol) in DCM (310 mL) cooled to -10° C. was added DIPEA (84.75 mL, 495.06 mmol). Then a solution of Pyr.SO3 complex (50%, 69.47 g, 218.25 mmol) in DMSO (225 mL) was slowly added. The reaction mixture was stirred for 2 h at 0° C. The reaction mixture was partitioned between water (150 mL) and DCM (220 mL). The two layers were separated and the aq. layer was extracted twice with DCM (2*150 mL). The combined org. layers were dried over Na2SO4, filtered and concentrated to dryness. The residue was co-evaporated 3 times with toluene and purified over a short pad of silica gel (EA-Hept. 2-1) to afford the title aldehyde as a white solid (33.58 g, 90% yield). MS (ESI, m/z): 230.0 [M+H+] or C11H19NO4. |
90% | With sulfur trioxide pyridine complex; N-ethyl-N,N-diisopropylamine In dichloromethane; dimethyl sulfoxide at -10℃; for 2h; | |
80% | Stage #1: 1,5-anhydro-2-[(tert-butoxycarbonyl)amino]-2,3,4-trideoxy-D-erythro-hexitol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 1h; Inert atmosphere; Stage #2: With N-ethyl-N,N-diisopropylamine In dichloromethane at -78 - 20℃; for 2h; Inert atmosphere; | 30.1 Dichloromethane (5 ml) and dimethyl sulfoxide (0.21 ml, 2.85 mmol) were mixed under nitrogen atmosphere, a dichloromethane (5 ml) solution of oxalyl chloride (0.21 ml, 2.50 mmol) was added dropwise at -78° C. and the resulting mixture was stirred for 30 minutes. A dichloromethane (5 ml) solution of the same starting material (440 mg, 1.90 mmol) as in Step 1 of Reference Example 2 was added dropwise at the same temperature and the resulting mixture was stirred for 1 hour. Then a dichloromethane (4 ml) solution of N,N-diisopropylethylamine (1.65 ml, 9.50 mmol) was added dropwise and the resulting mixture was stirred at the same temperature for 1 hour, warmed to room temperature, and further stirred for 1 hour. The reaction solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography [n-hexane:ethyl acetate=1:1→1:2 (v/v)] to give 347 mg (80%) of the title compound as a colorless solid.1H-NMR (400 MHz, CDCl3) δ: 1.36-1.44 (1H, m), 1.45 (9H, s), 1.53-1.63 (1H, m), 1.94-2.01 (1H, m), 2.10-2.17 (1H, m), 3.15 (1H, t, J=10.5 Hz), 3.59-3.67 (1H, m), 3.73 (1H, dd, J=11.0, 2.7 Hz), 4.17 (1H, dq, J=11.0, 2.1 Hz), 4.38 (1H, br s), 9.65 (1H, s). |
71% | Stage #1: 1,5-anhydro-2-[(tert-butoxycarbonyl)amino]-2,3,4-trideoxy-D-erythro-hexitol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane; dimethyl sulfoxide at -50℃; for 1h; Stage #2: With N-ethyl-N,N-diisopropylamine In dichloromethane; dimethyl sulfoxide at -40 - 20℃; for 3h; | 4 To a solution of oxalyl chloride (0.216 mL, 2.47 mmol) in dichloromethane (5 mL) at -50 °C was drop wise added a solution of dimethylsulfoxide (DMSO) (0.216 mL) in dichloromethane (5 mL). The mixture was stirred for 20 minutes, then a solution of tert-butyl [(3R,6S)-6- (hydroxymethyl)tetrahydro-2H-pyran-3-yl]carbamate (Intermediate 5, 440 mg, 1.9 mmol) in dichloromethane (5 mL) was added dropwise and the resulting mixture was stirred for one hour at -50 °C. A solution of diisopropylethyl amine (1.6 mL, 9.5 mmol) in dichloromethane (4 mL) was added dropwise, and the reaction mixture was allowed to warm to -40 °C and was stirred for 1 hour. The temperature of the reaction mixture was then allowed to reach room temperature over 2 hours. The solvent was evaporated under reduced pressure, and the residue was co- distilled once with toluene and then chromatographed on silica gel with hexanes/ ethyl acetate (1:1) to give 310 mg (71% yield) of product as a colorless solid. 1H-NMR (DMSO^6) S: 1.31-1.80 (m, 2H); 1.38 (s, 9H); 1.85-1.98 (m, 2H); 3.06 (dd,IH); 3.30-3.40 (m, IH, under HDO); 3.78 (dd, IH); 3.89 (m, IH); 6.85 (d, IH); 9.53 (s, IH). EPO |
Stage #1: 1,5-anhydro-2-[(tert-butoxycarbonyl)amino]-2,3,4-trideoxy-D-erythro-hexitol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 1.25h; Stage #2: With triethylamine In dichloromethane at -78 - 0℃; for 1h; | 24.24.i Example 24; 8-((lR,2R)-2-{(2S,5R)-5-[(^)-3-(2,5-difluoro-phenyl)-allylamino]- tetrahydro-pyr an-2-yl}- 1 ,2-dihydroxy-ethyl)-quinoline-2-carbonitrile; 24.i. (3R,6S)-(6-formyl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester; To a solution of oxalyl chloride (3.5 ml) in DCM (25 ml) cooled to -78°C, was added dropwise a solution of DMSO (3.5 ml) in DCM (25 ml). After 15 min stirring, a solution of (3i?,65)-(6-hydroxymethyl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester (prepared as described in Eur. J. Org. Chem. (2003), 2418-2427) in DCM (25 ml) was added dropwise. The reaction mixture was stirred 1 h and a solution of TEA (15 ml) in DCM (15 ml) was added dropwise. The reaction proceeded for 1 h, with warming to 00C. Saturated NaHCO3 (50 ml) was added. The org. layer was separated, dried over Na2SO4, filtered and concentrated in vacuo. The residue was chromatographed over SiO2 (Hex-EA 1-2) to afford the title aldehyde (2.5 g) as a colourless solid. | |
With sulfur trioxide pyridine complex; N-ethyl-N,N-diisopropylamine In dichloromethane; dimethyl sulfoxide at -10 - 20℃; for 6h; | tert-butyl ((3R,6S)-6-formyltetrahydro-2H-pyran-3-yl)carbamate To a solution of tert-butyl ((3R,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)carbamate (200 mg, 0.87 mmol) in DCM (5 mL) at -10° C. was added DIPEA (2.3 mL, 13 mmol) as a single portion followed by a solution of pyridine-SO3 (1:1) complex (2.1 g, 13 mmol) in DMSO (7 mL) dropwise over 2 minutes. Reaction vessel was transferred to a 0° C. bath and stirred for 1.5 hours then allowed to warm to room temperature over 2.5 hours. Reaction mixture was then brought to -10° C., pyridine-SO3 (1:1) complex (400 mg, 2.4 mmol) was added as a single portion, and the reaction mixture allowed to warm to room temperature over 2 hours. Upon completion, reaction mixture was poured into water (20 mL) and extracted with EtOAc (2*50 mL). The combined organic layers were washed with water (2*30 mL), dried over MgSO4, filtered, concentrated and the resulting crude aldehyde was carried forward without further purification. ES/MS: 230.0 [M+H]+ | |
Stage #1: 1,5-anhydro-2-[(tert-butoxycarbonyl)amino]-2,3,4-trideoxy-D-erythro-hexitol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 1.25h; Stage #2: With triethylamine In dichloromethane at -78 - 0℃; for 1h; | 29.a To a solution of oxalyl chloride (3.5 ml) in DCM (25 ml) cooled to -780C, was added drop wise a solution of DMSO (3.5 ml) in DCM (25 ml). After 15 minutes stirring, a solution of (3R, 6S)- (6-hydroxymethyl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester (prepared as described in Eur. J. Org. Chem. (2003), 2418-2427; 3 g) in DCM (25 ml) was added drop wise. The reaction was stirred 1 h and a solution of triethylamine (15 ml) in DCM (15 ml) was added dropwise. The reaction proceeded for 1 hour, with warming to O0C. Saturated sodium bicarbonate (50 ml) was added. The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was chromatographed (Ηex/EtOAc 1:2) to afford the title aldehyde (2.5 g) as a colorless solid. | |
Stage #1: 1,5-anhydro-2-[(tert-butoxycarbonyl)amino]-2,3,4-trideoxy-D-erythro-hexitol With oxalyl dichloride In dichloromethane at -78℃; for 1h; Stage #2: With triethylamine In dichloromethane at -78 - 0℃; for 1h; | 29.a 29.a) (3R,6S)-(6-formyl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester To a solution of oxalyl chloride (3.5 ml) in DCM (25 ml) cooled to -78° C., was added drop wise a solution of DMSO (3.5 ml) in DCM (25 ml). After 15 minutes stirring, a solution of (3R,6S)-(6-hydroxymethyl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester (prepared as described in Eur. J. Org. Chem. (2003), 2418-2427; 3 g) in DCM (25 ml) was added drop wise. The reaction was stirred 1 h and a solution of triethylamine (15 ml) in DCM (15 ml) was added dropwise. The reaction proceeded for 1 hour, with warming to 0° C. Saturated sodium bicarbonate (50 ml) was added. The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was chromatographed (Hex/EtOAc 1:2) to afford the title aldehyde (2.5 g) as a colorless solid. | |
With Dess-Martin periodane In dichloromethane at 0 - 25℃; for 15h; Inert atmosphere; | tert-butyl 7V-[(3R,6S)-6-formyltetrahydropyran-3-yl]carbamate: To a mixture of tert-butyl N-[(3R,6S)-6-(hydroxymethyl)tetrahydropyran-3-yljcarbamate (4.0 g, 17.3 mmol) in DCM (40 mL) was added Dess-Martin periodinane (8.07 g, 19.0 mmol) at 0 °C under N2 and the mixture was stirred at25 °C for 15 h. The reaction mixture was diluted with sat. NaHCO3 and was filtered. The aqueous phase was extracted with EtOAc (3 x 10 mL), the combined organic phases were washed with brine (5 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide tert-butyl N-[(3R,6S)-6-formyltetrahydropyran-3-yljcarbamate. ‘H-NMR (400 MHz, CDC13): 9.58 - 9.77 (m, 1 H), 4.41 (brs, 1 H), 4.14 -4.21 (m, 1 H), 3.73 (dd,J= 10.79, 2.89 Hz, 1 H), 3.15 (brt,J=10.35 Hz, 1 H), 2.09 -2.17 (m, 1 H), 1.98 (br dd, J= 13.49, 3.20 Hz, 1 H), 1.51 - 1.63 (m, 1 H), 1.44 (s, 9 H), 1.33 - 1.41 (m, 1 H), 1.33 - 1.41 (m, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With hydrogen In ethyl acetate for 3h; | B.ii To a well-stirred solution of intermediate Bi. (112 g, 488 mmol) in EA (1.2 L) was added platinum oxide (5 g). The reaction was evacuated twice and back-filled with hydrogen. The reaction proceeded 3 h supplying hydrogen when needed. Upon completion, the reaction mixture was filtered through plug of Celite. The filtrate was concentrated to dryness and the residue was resuspended in diisopropylether (200 mL) and Hept (800 mL). After stirring for 1 h, the slurry was cooled to 00C for one hour, filtered and the solid was washed with Hept and dried in vacuo to yield the title alcohol as a white solid (104 g, 92% yield). 1H NMR (CDCl3) δ: 4.25 (br. s, IH); 4.11 (m, IH); 3.60 (dd, J = 3.4, 11.5 Hz, 2H); 3.53 (m, IH); 3.37 (m, 1 H); 3.02 (t, J = 10.7 Hz, IH); 2.10 (m, IH); 1.83 (br. s, IH); 1.62 (m, IH); 1.49 (m, IH); 1.44 (s, 9H); 1.32 (m, IH). |
80% | With hydrogen In ethyl acetate at 20℃; for 5h; | 5 tert-butyl [(3R,6S)-6-(hydroxymethyl)-3,6-diliydro-2H-pyran-3-yl]carbamate(Intermediate 6, 0.6g, 2.62 mmol) was hydrogenated in ethyl acetate (10 mL) at room temperature and normal pressure over palladium/charcoal (10%, wet) for 5 hours. The reaction mixture was filtered through a 0.45 μm membrane and solvent was evaporated under reduced pressure. Chromatography on silica gel with ethyl acetate/ hexanes (1:1 to 2:1) gave 0.486 g (80% yield) of the product as a colorless solid.1H-NMR (DMSO-d6) δ: 1.21 (m, IH); 1.30-1.42 (m, IH); 1.38 (s, 9H); 1.64 (m, IH); 1.84 (m, IH); 2.92 (dd, IH); 3.14 (m, IH); 3.25-3.38 (m, 3H, under HDO); 3.78 (m, IH); 4.59 (dd, IH); 6.74 (d, IH).MS (ESP): 254(MNa+) for C11H2INO3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; triethylamine In dichloromethane at 20℃; for 4h; | G.G.i Preparation G; (3R,6S)-[6-(l-phenyl-lH-tetrazole-5-sulfonylmethyl)-tetrahydro-pyran- 3-yl]-carbamic acid tert-butyl ester; Gi. toluene-4-sulfonic acid (2S,5R)-5-tert-butoxycarbonylamino-tetrahydro-pyran-2-ylmethyl ester; To an ice-chilled solution of (3i?,65)-(6-hydroxymethyl-tetrahydro-pyran-3-yl)-carbamic acid tert-bvXy ester (obtained as described in Eur. J. Org. Chem. (2003); 25 g, 108 mmol) in DCM (650 ml) were added TEA (30 ml), DMAP (1.8 g) and TsCl (22.6 g). The reaction was stirred at rt for 4 h. Saturated NaHCO3 (100 ml) was added. The volatiles were removed under reduced pressure and the residue was taken up in EA (400 ml). The org. layer was washed with saturated CuSO4 (2 x 150 ml), water (3 x 150 ml) and brine (100 ml). The org. layer was dried over Na2SO4, filtered and concentrated to dryness to afford after drying a white solid (41.8 g) that was carried on without further purification. | |
75.83 g | With dmap; triethylamine In dichloromethane for 4h; Cooling with ice; | |
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 4h; | B.iii To an ice-chilled solution of intermediate B.ii (40.9 g, 176.8 mmol) in DCM (840 mL) were added successively TEA (59.5 mL, 423.9 mmol), DMAP (3.01 g, 24.56 mmol) and TsCl (42.4 g, 222.4 mmol). The reaction proceeded 4 h with warming to rt. Aq. sat NaHCO3 (350 mL) was added. The two phases were separated and the org. layer was evaporated under reduced pressure. The residue was diluted with EA (900 mL) and the org. layer was washed three times with aq. sat. CuSO4 (3 x 200 mL), brine (200 mL), dried over MgSO4, filtered and concentrated to dryness to afford after drying under HV the title tosylate (75.83 g, 196.7 mmol).1H NMR (CDCl3) δ: 7.78 (d, J = 8.7 Hz, 2H); 7.33 (d, J = 8.7 Hz, 2H); 4.20 (m, IH); 4.01 (m, IH); 3.96 (d, J = 5.7 Hz, 2H); 3.54 (br s, IH); 3.48 (m, IH); 2.93 (t, J = 10.8 Hz, IH); 2.44 (s, 3H); 2.09 (m, IH); 1.69 (m, IH); 1.48-1.18 (m, 2H); 1.42 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrogenchloride In 1,4-dioxane; methanol at 20℃; for 1h; | 2.1 1,5-Anhydro-2-[(tert-butoxycarbonyl)amino]-2,3,4-trideoxy-D-erythro-hexitol (Eur. J. Org. Chem., 2003, 2418-2427) (6.00 g, 0.03 mol) was dissolved in methanol (20 ml), 4N hydrochloric acid/1,4-dioxane solution (60 ml) was added and the resulting mixture was stirred at room temperature for 1 hour. The reaction solvent was evaporated under reduced pressure to give 4.5 g (100%) of the title compound as a colorless solid.1H-NMR (400 MHz, DMSO-d6) δ: 1.25 (1H, ddd, J=24.3, 13.3, 3.7 Hz), 1.52 (1H, ddd, J=24.7, 12.4, 3.9 Hz), 1.66-1.72 (1H, m), 2.03-2.09 (1H, m), 2.97-3.06 (1H, m), 3.19-3.37 (4H, m), 3.96-4.00 (1H, m).MS (ESI) m/z: 132 (M+H)+. |
100% | With hydrogenchloride In 1,4-dioxane at 20℃; for 3h; | 10.1 Step 1: Synthesis of compound 10-2 Add compound 10-1 (2.0g, 8.65mmol,With reference to the literature Eur. J. Org. Chem. 2003, prepared by 2418-2427) and hydrogen chloride dioxane solution (20 mL), the reaction solution was stirred and reacted at room temperature for 3 hours. TLC showed that the reaction of the raw materials was complete. The reaction liquid was directly evaporated to dryness under vacuum to obtain 1.5 g of product 10-2, yield: 100%. The product was used directly in the next step without purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane; methanol / 1 h / 20 °C 2: sodium hydroxide / water / 16 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: hydrogenchloride / 1,4-dioxane; methanol / 1 h / 20 °C 2: sodium hydroxide / water / 16 h / 0 - 20 °C 3: hydrogen / palladium 10% on activated carbon / methanol / 4 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1 h / -78 °C / Inert atmosphere 1.2: 2 h / -78 - 20 °C / Inert atmosphere 2.1: diethyl ether; tetrahydrofuran / 16 h / 0 - 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: hydrogenchloride / 1,4-dioxane; methanol / 1 h / 20 °C 2: sodium hydroxide / water / 16 h / 0 - 20 °C 3: hydrogen / palladium 10% on activated carbon / methanol / 4 h / 20 °C 4: triethylamine / methanol / 120 h / 50 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: hydrogenchloride / 1,4-dioxane; methanol / 1 h / 20 °C 2: sodium hydroxide / water / 16 h / 0 - 20 °C 3: hydrogen / palladium 10% on activated carbon / methanol / 4 h / 20 °C 4: sulfolane / 28 h / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate; sodium hypochlorite; Aliquat 336; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / Isopropyl acetate / 1.5 h / 0 - 10 °C 1.2: 1.5 h / 5 - 10 °C 2.1: pivaloyl chloride; 4-methyl-morpholine / dichloromethane / 0.5 h / 20 °C / Cooling |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: sodium hydrogencarbonate; sodium hypochlorite; Aliquat 336; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / Isopropyl acetate / 1.5 h / 0 - 10 °C 1.2: 1.5 h / 5 - 10 °C 2.1: pivaloyl chloride; 4-methyl-morpholine / dichloromethane / 0.5 h / 20 °C / Cooling 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 3.5 h / -10 - 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: sodium hydrogencarbonate; sodium hypochlorite; Aliquat 336; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / Isopropyl acetate / 1.5 h / 0 - 10 °C 1.2: 1.5 h / 5 - 10 °C 2.1: pivaloyl chloride; 4-methyl-morpholine / dichloromethane / 0.5 h / 20 °C / Cooling 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 3.5 h / -10 - 0 °C 4.1: hydrogenchloride / isopropyl alcohol / 3 h / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: sodium hydrogencarbonate; sodium hypochlorite; Aliquat 336; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / Isopropyl acetate / 1.5 h / 0 - 10 °C 1.2: 1.5 h / 5 - 10 °C 2.1: pivaloyl chloride; 4-methyl-morpholine / dichloromethane / 0.5 h / 20 °C / Cooling 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 3.5 h / -10 - 0 °C 4.1: hydrogenchloride / isopropyl alcohol / 3 h / 40 °C 5.1: sodium hydrogencarbonate / water; tetrahydrofuran; acetone / 1.5 h / 4 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: sodium hydrogencarbonate; sodium hypochlorite; Aliquat 336; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / Isopropyl acetate / 1.5 h / 0 - 10 °C 1.2: 1.5 h / 5 - 10 °C 2.1: pivaloyl chloride; 4-methyl-morpholine / dichloromethane / 0.5 h / 20 °C / Cooling 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 3.5 h / -10 - 0 °C 4.1: hydrogenchloride / isopropyl alcohol / 3 h / 40 °C 5.1: triethylamine / dichloromethane / 1.5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: sodium hydrogencarbonate; sodium hypochlorite; Aliquat 336; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / Isopropyl acetate / 1.5 h / 0 - 10 °C 1.2: 1.5 h / 5 - 10 °C 2.1: pivaloyl chloride; 4-methyl-morpholine / dichloromethane / 0.5 h / 20 °C / Cooling 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 3.5 h / -10 - 0 °C 4.1: diisobutylaluminium hydride / tetrahydrofuran / 1.5 h / -75 - -68 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: sodium hydrogencarbonate; sodium hypochlorite; Aliquat 336; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / Isopropyl acetate / 1.5 h / 0 - 10 °C 1.2: 1.5 h / 5 - 10 °C 2.1: pivaloyl chloride; 4-methyl-morpholine / dichloromethane / 0.5 h / 20 °C / Cooling 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 3.5 h / -10 - 0 °C 4.1: diisobutylaluminium hydride / tetrahydrofuran / 1.5 h / -75 - -68 °C 5.1: hydrogenchloride / isopropyl alcohol / 1.17 h / 60 - 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: sodium periodate; ruthenium trichloride / water; acetonitrile / 20 °C 2: dicyclohexyl-carbodiimide; ammonia; 1-hydroxy-pyrrolidine-2,5-dione / ethyl acetate / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2.1: sodium iodide / acetone / 24 h / Reflux 3.1: potassium hydroxide / ethanol / 1 h / Reflux 4.1: dihydrogen peroxide; hexaammonium heptamolybdate tetrahydrate / tetrahydrofuran; water; ethanol / 3 h / 20 - 65 °C 5.1: potassium hexamethylsilazane / 1,2-dimethoxyethane; toluene / 0.5 h / -60 °C 6.1: methanesulfonamide / ethyl acetate; water; <i>tert</i>-butyl alcohol 7.1: trifluoroacetic acid / 1 h / 20 °C 8.1: methanol; 1,2-dichloro-ethane / 50 °C / Molecular sieve 8.2: 2 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2.1: sodium iodide / acetone / 24 h / Reflux 3.1: potassium hydroxide / ethanol / 1 h / Reflux 4.1: dihydrogen peroxide; hexaammonium heptamolybdate tetrahydrate / tetrahydrofuran; water; ethanol / 3 h / 20 - 65 °C 5.1: lithium hexamethyldisilazane / tetrahydrofuran; 1,2-dimethoxyethane / 0.5 h / -60 °C 6.1: methanesulfonamide / ethyl acetate; water; <i>tert</i>-butyl alcohol 7.1: trifluoroacetic acid / 1 h / 20 °C 8.1: methanol; 1,2-dichloro-ethane / 50 °C / Molecular sieve 8.2: 2 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2.1: sodium iodide / acetone / 24 h / Reflux 3.1: potassium hydroxide / ethanol / 1 h / Reflux 4.1: dihydrogen peroxide; hexaammonium heptamolybdate tetrahydrate / tetrahydrofuran; water; ethanol / 3 h / 20 - 65 °C 5.1: lithium hexamethyldisilazane / tetrahydrofuran; 1,2-dimethoxyethane / 0.5 h / -60 °C 6.1: methanesulfonamide / ethyl acetate; water; <i>tert</i>-butyl alcohol 7.1: trifluoroacetic acid / 1 h / 20 °C 8.1: methanol / 20 °C 8.2: 0.67 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2.1: sodium iodide / acetone / 24 h / Reflux 3.1: potassium hydroxide / ethanol / 1 h / Reflux 4.1: dihydrogen peroxide; hexaammonium heptamolybdate tetrahydrate / tetrahydrofuran; water; ethanol / 3 h / 20 - 65 °C 5.1: lithium hexamethyldisilazane / tetrahydrofuran; 1,2-dimethoxyethane / 0.5 h / -60 °C 6.1: methanesulfonamide / ethyl acetate; water; <i>tert</i>-butyl alcohol 7.1: trifluoroacetic acid / 1 h / 20 °C 8.1: methanol / 20 °C 8.2: 0.67 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2.1: sodium iodide / acetone / 24 h / Reflux 3.1: potassium hydroxide / ethanol / 1 h / Reflux 4.1: dihydrogen peroxide; hexaammonium heptamolybdate tetrahydrate / tetrahydrofuran; water; ethanol / 3 h / 20 - 65 °C 5.1: lithium hexamethyldisilazane / tetrahydrofuran; 1,2-dimethoxyethane / 0.5 h / -60 °C 6.1: methanesulfonamide / ethyl acetate; water; <i>tert</i>-butyl alcohol 7.1: trifluoroacetic acid / 1 h / 20 °C 8.1: methanol / 20 °C 8.2: 0.67 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2.1: sodium iodide / acetone / 24 h / Reflux 3.1: potassium hydroxide / ethanol / 1 h / Reflux 4.1: dihydrogen peroxide; hexaammonium heptamolybdate tetrahydrate / tetrahydrofuran; water; ethanol / 3 h / 20 - 65 °C 5.1: lithium hexamethyldisilazane / tetrahydrofuran; 1,2-dimethoxyethane / 0.5 h / -60 °C 6.1: methanesulfonamide / ethyl acetate; water; <i>tert</i>-butyl alcohol 7.1: trifluoroacetic acid / 1 h / 20 °C 8.1: methanol / 20 °C 8.2: 0.67 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2.1: sodium iodide / acetone / 24 h / Reflux 3.1: potassium hydroxide / ethanol / 1 h / Reflux 4.1: dihydrogen peroxide; hexaammonium heptamolybdate tetrahydrate / tetrahydrofuran; water; ethanol / 3 h / 20 - 65 °C 5.1: lithium hexamethyldisilazane / tetrahydrofuran; 1,2-dimethoxyethane / 0.5 h / -60 °C 6.1: methanesulfonamide / ethyl acetate; water; <i>tert</i>-butyl alcohol 7.1: trifluoroacetic acid / 1 h / 20 °C 8.1: methanol / 20 °C 8.2: 0.67 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2.1: sodium iodide / acetone / 24 h / Reflux 3.1: potassium hydroxide / ethanol / 1 h / Reflux 4.1: dihydrogen peroxide; hexaammonium heptamolybdate tetrahydrate / tetrahydrofuran; water; ethanol / 3 h / 20 - 65 °C 5.1: lithium hexamethyldisilazane / tetrahydrofuran; 1,2-dimethoxyethane / 0.5 h / -60 °C 6.1: methanesulfonamide / ethyl acetate; water; <i>tert</i>-butyl alcohol 7.1: trifluoroacetic acid / 1 h / 20 °C 8.1: methanol / 20 °C 8.2: 0.67 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2.1: sodium iodide / acetone / 24 h / Reflux 3.1: potassium hydroxide / ethanol / 1 h / Reflux 4.1: dihydrogen peroxide; hexaammonium heptamolybdate tetrahydrate / tetrahydrofuran; water; ethanol / 3 h / 20 - 65 °C 5.1: lithium hexamethyldisilazane / tetrahydrofuran; 1,2-dimethoxyethane / 0.5 h / -60 °C 6.1: methanesulfonamide / ethyl acetate; water; <i>tert</i>-butyl alcohol 7.1: trifluoroacetic acid / 1 h / 20 °C 8.1: methanol / 20 °C 8.2: 0.67 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2: sodium iodide / acetone / 24 h / Reflux | ||
Multi-step reaction with 2 steps 1: dmap; triethylamine / dichloromethane / 4 h / 0 - 20 °C 2: sodium iodide / acetone / 24 h / Heating / reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2: sodium iodide / acetone / 24 h / Reflux 3: potassium hydroxide / ethanol / 1 h / Reflux | ||
Multi-step reaction with 3 steps 1.1: dmap; triethylamine / dichloromethane / 4 h / 0 - 20 °C 2.1: sodium iodide / acetone / 24 h / Heating / reflux 3.1: potassium hydroxide / ethanol / 1 h / Heating / reflux 3.2: Heating / reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: triethylamine; dmap / dichloromethane / 4 h / Cooling with ice 2: sodium iodide / acetone / 24 h / Reflux 3: potassium hydroxide / ethanol / 1 h / Reflux 4: dihydrogen peroxide; hexaammonium heptamolybdate tetrahydrate / tetrahydrofuran; water; ethanol / 3 h / 20 - 65 °C | ||
Multi-step reaction with 4 steps 1.1: dmap; triethylamine / dichloromethane / 4 h / 0 - 20 °C 2.1: sodium iodide / acetone / 24 h / Heating / reflux 3.1: potassium hydroxide / ethanol / 1 h / Heating / reflux 3.2: Heating / reflux 4.1: ammonium heptamolybdate; dihydrogen peroxide / tetrahydrofuran; ethanol; water / 3 h / 20 - 65 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran; N,N-dimethyl-formamide / 4 h / 20 °C 2: trifluoroacetic acid / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran; N,N-dimethyl-formamide / 4 h / 20 °C 2.1: trifluoroacetic acid / 1 h / 20 °C 3.1: methanol; 1,2-dichloro-ethane / 50 °C / Molecular sieve 3.2: 2 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran; N,N-dimethyl-formamide / 4 h / 20 °C 2.1: trifluoroacetic acid / 1 h / 20 °C 3.1: methanol; 1,2-dichloro-ethane / 50 °C / Molecular sieve 3.2: 2 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: sodium periodate; ruthenium trichloride / water; acetonitrile / 20 °C 2: dicyclohexyl-carbodiimide; ammonia; 1-hydroxy-pyrrolidine-2,5-dione / ethyl acetate / 20 °C 3: caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; tris(dibenzylideneacetone)dipalladium(0) chloroform complex / 1,4-dioxane / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: sodium periodate; ruthenium trichloride / water; acetonitrile / 20 °C 2: dicyclohexyl-carbodiimide; ammonia; 1-hydroxy-pyrrolidine-2,5-dione / ethyl acetate / 20 °C 3: caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; tris(dibenzylideneacetone)dipalladium(0) chloroform complex / 1,4-dioxane / 100 °C 4: trifluoroacetic acid / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: sodium periodate; ruthenium trichloride / water; acetonitrile / 20 °C 2.1: dicyclohexyl-carbodiimide; ammonia; 1-hydroxy-pyrrolidine-2,5-dione / ethyl acetate / 20 °C 3.1: caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; tris(dibenzylideneacetone)dipalladium(0) chloroform complex / 1,4-dioxane / 100 °C 4.1: trifluoroacetic acid / 1 h / 20 °C 5.1: methanol; 1,2-dichloro-ethane / 50 °C / Molecular sieve 5.2: 2 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1,5-anhydro-2-[(tert-butoxycarbonyl)amino]-2,3,4-trideoxy-D-erythro-hexitol With sodium hydride; sodium iodide In N,N-dimethyl-formamide; mineral oil at 0 - 15℃; for 0.5h; Inert atmosphere; Stage #2: (3-cis-(trifluoromethoxy)cyclobutyl)methyl methanesulfonate In N,N-dimethyl-formamide; mineral oil at 0 - 15℃; for 12h; Inert atmosphere; | 9 tert-butyl ((3R, 6S)-6-(((3-cis-(trifiuoromethoxy)cyclobutyl)methoxy)methyl)tetrahydro-2H- pyran-3-yl)carbamate To a solution of tert-butyl N- [(3R,6S)-6-(hydroxymethyl)tetrahydropyran-3 - yljcarbamate (200 mg, 0.86 mmol) in DMF (2 mL) was added NaH (69 mg, 1.73 mmol, 60% by wt.) and NaT (130 mg, 0.86 mmol) at 0 °C. After addition, the mixture was stirred at 15 °C for 30 mm, and then (3 -cis-(trifluoromethoxy)cyclobutyl)methyl methanesulfonate (172 mg, 0.69 mmol) was added dropwise at 0 °C and the resulting mixture was stirred at 15 °C for 12 h. The reaction mixture was diluted with saturated aqueous NH4C1 (10 mL) at 0 °C, and then extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with H20 (3 x 5 mL), brine (3 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (PE:EtOAc = 20:1 to 0:1) to give tert-butyl ((3R,6S)-6-(((3-cis- (trifluoromethoxy)cyclobutyl)methoxy)methyl)tetrahydro-2H-pyran-3 -yl)carbamate. ‘H-NMR (400 MHz, CDC13): 4.47 -4.64 (m, 1 H), 4.22 (d, J= 5.95 Hz, 1 H), 4.10 (br dd, J 10.80, 2.43 Hz, 1 H), 3.60 (br d, J 16.98 Hz, 2 H), 3.30-3.51 (m, 4 H), 2.96-3.08 (m, 1 H), 2.47 (dt, J= 11.69, 7.28 Hz, 2 H), 2.07 -2.25 (m, 2 H), 1.91 -2.05 (m, 2 H), 1.71 (br d, J= 13.89 Hz, 1 H), 1.42 - 1.48 (m, 9 H),1.22 - 1.36 (m, 2 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 55h; | 22 1,5-Anhydro-2-[(tert-butoxycarbonyl)amino]-6-O-[tert-butyl(diphenyl)silyl]-2,3,4-trideoxy-D-erythro-hexitol 1,5-Anhydro-2-[(tert-butoxycarbonyl)amino]-2,3,4-trideoxy-D-erythro-hexitol (CAS Registry Number: 603130-12-7, WO2006125974) (3 g, 13.0 mmol) and imidazole (1.77 g, 25.9 mmol) were dissolved in N,N-dimethylformamide (25 mL). To this, tert-butyldiphenylchlorosilane (3.74 g, 13.6 mmol) was added dropwise at room temperature, and the mixture was stirred at room temperature for 55 hours. To the reaction mixture, ethyl acetate and water were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated saline and dried over anhydrous magnesium sulfate. The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography [elution solvent: hexane/ethyl acetate=19/1-7/3 (V/V)] to obtain the title compound (6.72 g (yield: 100%)) as a colorless oily substance. |
Tags: 603130-12-7 synthesis path| 603130-12-7 SDS| 603130-12-7 COA| 603130-12-7 purity| 603130-12-7 application| 603130-12-7 NMR| 603130-12-7 COA| 603130-12-7 structure
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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.
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