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CAS No. : | 5470-84-8 | MDL No. : | MFCD11553544 |
Formula : | C11H14O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 178.23 | Pubchem ID : | - |
Synonyms : |
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Signal Word: | Class: | ||
Precautionary Statements: | UN#: | ||
Hazard Statements: | Packing Group: |
* 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 |
---|---|---|
100% | With Dess-Martin periodane In dichloromethane at 20℃; for 1.5h; | |
99% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78℃; for 2h; | |
99% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane for 1.25h; Cooling; Schlenk technique; Inert atmosphere; |
98% | Stage #1: 4-benzyloxy-butan-1-ol With phosphorus pentoxide; dimethyl sulfoxide In dichloromethane at 0 - 20℃; for 2.5h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane at 0℃; for 0.5h; | |
97% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; | |
96% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78℃; for 3h; | |
96% | With pyridinium chlorochromate In dichloromethane at 0 - 25℃; for 3.75h; | 17.1 Example 17; 5-cvclopropyl-2-(4-fluorophenyl)-6-(N-((2-hvdroxy-1 ,2-oxaborinan-4- l)methyl)methylsulfonamido)-N-methylbenzofuran-3-carboxamideStep 1: 4-(benzyloxy)butanalA solution of 4-(benzyloxy)butan-1-ol (10 g, 55.5 mmol) in anhydrous DCM (50ml_) at 0 °C was treated with PCC (17.94 g, 83.2 mmol) and the mixture was stirred for 45 mins. The mixture was allowed warm to 25 °C and stirred for 3 h. The suspension was filtered through celite, concentrated, and purified by column chromatography to give 4-(benzyloxy)butanal (9.5 g, 96% yeild). |
95.3% | With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dimethyl sulfoxide at 25℃; for 2h; | |
94% | With sulphur trioxide pyridine complex; triethylamine In dichloromethane; dimethyl sulfoxide at 20℃; for 1h; | |
93% | With 2,2,6,6-tetramethyl-1-piperidinyloxy free radical; sodium chlorine monoxide; potassium bromide In dichloromethane cooling; | |
93% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; | |
93% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; phenyliodine(III) diacetate In dichloromethane at 25℃; for 1h; | 4-(benzyloxy)butanal To a solution ofthe alcohol 8 (15.0 g, 83.2 mmol) indry CH2Cl2 (150 mL) was added in one portion bis-acetoxyiodobenzene(29.46 g, 91.5 mmol) and TEMPO (1.29 g, 8.3 mmol). The reactionmixture was stirred for 1 h at 25 °C followed by quenching with saturatedsolution of aq. ammonium thiosulphate. The organic layer was separated, washedwith brine and subjected to column chromatographic purification with Pet Ether:EtOAc (9.5:0.5) to afford the brown oil of aldehyde 9. Yield:13.8 g (93%); IR (CHCl3, cm-1): 2937, 2861, 1724, 1105, 744; 1HNMR (200 MHz, CDCl3)d 9.77 (t, J = 1.6 Hz,1H), 7.30 ( m, 5H), 4.47 (s, 2H), 3.49 (t, J=6 Hz, 2H), 2.43-2.58 (m, 2H), 1.87-2.0 (q, J = 6Hz, 2H); 13C NMR (50 MHz,CDCl3) d 201.7,138.2, 128.3, 127.4, 72.9, 69.0, 40.9, 22.6; Anal. Calcd. for C11H14O2: C, 74.13; H, 7.92.Found: C, 74.06; H, 7.78%. |
92% | With 4-hydroxy-TEMPO benzoate; sodium bromide In dichloromethane; water monomer NaHCO3-buffered at pH 8.6; electrolysis; | |
92% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 0℃; | |
92% | With pyridinium chlorochromate In dichloromethane at 20℃; for 1h; | |
92% | With pyridinium chlorochromate In dichloromethane at 0 - 20℃; | 24 4.1.24 4-(Benzyloxy)butanal 22 To stirred solution of alcohol 21 (10 g, 55.5 mmol) in dichloromethane (150 mL) at 0 °C were added pyridinium chlorochromate (17.96 g, 83.33 mmol) and Celite (17.96 g) and stirred at room temperature for 5 h. Diethyl ether (100 mL) was added and the reaction mixture was filtered through a small pad of Celite and silica gel. The filtered cake was washed thoroughly with ether (2 × 150 mL) and the filtrate was concentrated under reduced pressure. After flash column chromatography on silica gel (100-200 mesh, eluent: 8% EtOAc in hexane) aldehyde 22 (9.09 g, 92%) was obtained as a colorless liquid. 1H NMR (400 MHz, CDCl3): δ 9.76 (t, J = 1.5 Hz, 1H), 7.36-7.17 (m, 5H), 4.46 (s, 2H), 3.47 (q, J = 5.1 Hz, 2H), 2.53 (td, J = 7.0, 1.5 Hz, 2H), 1.92 (ddd, J = 13.0, 7.0, 6.0 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 201.3, 138.2, 128.4, 127.6, 73.0, 69.0, 41.0, 22.6; MASS (EIMS): m/z 178 (M)+. |
90% | With piridinium dichromate In dichloromethane for 5h; | |
90% | Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 0.333333h; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; | |
90% | With sodium chlorine monoxide; 4-([4-(triphenylphosphonio)benzyl]oxy}carbonyl)oxy-2,2,6,6-tetramethylpiperidin-1-oxyl perchlorate; Sodium hydrogenocarbonate; potassium bromide In dichloromethane; water monomer for 0.166667h; | |
90% | With pyridinium chlorochromate In dichloromethane at 0 - 20℃; | |
89% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 0℃; for 0.75h; | |
89% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; | |
89% | With 2-iodoxybenzoic acid In dimethyl sulfoxide at 20℃; for 2h; Inert atmosphere; | |
89% | With sodium chlorine monoxide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; Sodium hydrogenocarbonate; potassium bromide Inert atmosphere; | |
88% | With pyridinium chlorochromate In dichloromethane | |
88% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78℃; | |
88% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane | |
87% | With oxalyl dichloride; triethylamine In dichloromethane; dimethyl sulfoxide at 20℃; | |
87% | With pyridinium chlorochromate In dichloromethane at 20℃; for 3h; | |
87% | With oxalyl dichloride; triethylamine In dichloromethane; dimethyl sulfoxide at -70 - 20℃; for 2.25h; | |
87% | With dimethyl sulfoxide; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dichloromethane at 0 - 20℃; for 4h; | |
87% | With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dichloromethane; dimethyl sulfoxide at 0 - 20℃; for 4h; | |
86% | With Dess-Martin periodane In dichloromethane | |
85% | Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 1h; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; for 1.5h; | 4-(Benzyloxy)butanal (6b) Toa solution of oxalyl chloride (17.25 mL, 198.25 mmol) in CH2Cl2(200 mL) at -78 °C was added DMSO (28.6 mL, 396.5 mmol) and the resultant solutionstirred at the same temperature for 30 min. To it was added the solution ofalcohol 6a (17.84 g, 99.122 mmol) inCH2Cl2 (50 mL) dropwise at -78 °C and resulting cloudywhite mixture was stirred for 1 h and was treated with triethylamine (83.0 mL, 594.73mmol) and stirred for 30 min at the same temperature. The reaction mixture was stirredat 0 °C for 40 min and at room temperature for 20 min and then quenched withsaturated NaHCO3 (100 mL). The layers were separated and the aqueouslayer was extracted with CH2Cl2 (3 x 100 mL), thecombined organic layers were dried over Na2SO4, andconcentrated in vacuo. Purification by column chromatography on small pad of silicagel (EtOAc/hexanes, 1:19) gave the aldehyde 6b (15.0 g, 85%) as a oily yellow liquid. 1H NMR (300 MHz, CDCl3) δ 9.79 (s, 1H), 7.39-7.25 (m, 5H), 4.50 (s, 2H), 3.51(t, J = 6.0 Hz, 2H), 2.55 (t, J = 7.5 Hz, 2H), 2.0-1.90 (m, 2H); 13CNMR (75 MHz, CDCl3) δ 202.0, 138.2, 128.0, 127.3, 127.2, 72.5, 68.8,40.5, 22.2; IR (neat): nmax 2931, 2862, 1720, 1511, 1412, 1365, 1260, 1100,1030, 740, 699, 600 cm-1; ESI-MS (m/z): 201 (M+Na)+. |
83% | Stage #1: 4-benzyloxy-butan-1-ol With dimethyl sulfoxide; trifluoroacetic anhydride In dichloromethane at -78℃; for 1h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; for 1h; Inert atmosphere; | |
83% | With dimethyl sulfoxide; trifluoroacetic anhydride | 1 The prepared intermediate (S) - (-) - 2-methyl-1-butanol was dissolved in trifluoroacetic anhydride (Swern Oxidation) in anhydrous TFAA and dimethyl sulfoxide (DMSO) To give 4- (benzyloxy) butanal in a yield of 83%. |
80% | With p-CO2H-IBX In N,N-dimethyl-formamide at 55 - 60℃; for 4h; | |
80% | With pyridinium chlorochromate In dichloromethane at 20℃; for 12h; | |
79% | With pyridinium chlorochromate In dichloromethane at 0 - 25℃; | |
79% | With pyridinium chlorochromate In dichloromethane at 0 - 25℃; for 3.75h; | P General Procedure P. A solution of the alcohol (1 equiv) in anhydrous CH2Cl2 (0.2 M) at 0 0C was treated with PCC (1.5 equiv) and the mixture was stirred for 45 min. The reaction mixture was allowed to warm at 25 °C and stirred for 3 h. The suspension was filtered through Celite and concentrated. Column chromatography (SiO2) afforded the aldehyde.; 4-(Benzyloxy)butan-l-ol was oxidized to 4-(benzyloxy)butanal (7.35 g, 79%) following general procedure P |
77% | With 2,2,6,6-tetramethyl-1-piperidinyloxy free radical; sodium chlorine monoxide; benzyl-triethyl-ammonium chloride; Sodium hydrogenocarbonate; sodium chloride; potassium bromide In dichloromethane; water monomer for 0.166667h; | |
77% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium bromide In Isopropyl acetate at 0℃; for 3.5h; | |
76% | With pyridinium chlorochromate In dichloromethane for 2h; | |
75.5% | With 2,2,6,6-tetramethyl-1-piperidinyloxy free radical; sodium chlorine monoxide; Sodium hydrogenocarbonate In water monomer; ethyl acetate at 15℃; for 2h; | |
75% | Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -55℃; for 0.25h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane at -55℃; for 0.25h; Inert atmosphere; | |
75% | Stage #1: 4-benzyloxy-butan-1-ol With phosgene; dimethyl sulfoxide In dichloromethane at -78℃; for 0.25h; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; for 0.333333h; | |
72% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78℃; for 4h; Inert atmosphere; | |
71% | Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 2h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; Inert atmosphere; | (S)-4-(Benzyloxy)-2-fluorobutanal (M1) and 4-(Benzyloxy)-2,2-difluorobutanal (M2) Step 1: To a solution of oxalyl chloride (0.4 mL, 5.0 mmol) indry DCM (3.6 mL) at -788C was added DMSO (0.5 mL,6.7 mmol). After 20 min, a solution of 4-(benzyloxy)butan-1-ol(0.5 g, 2.8 mmol) in dry DCM (1.2 mL) was added dropwise tothe reaction mixture before being left to stir for 2 h at -788C.Triethylamine (1.6 mL, 11 mmol) was added and the reactionwas warmed to room temperature and diluted withDCM(4 mL).The organic layer was washed with saturated NH4Cl solution(5 mL) and water (35 mL), dried over MgSO4, filtered, andconcentrated under reduced pressure. The crude product waspurified by flash chromatography eluting with hexane/EtOAc(85 : 15) to yield 4-(benzyloxy)butanal as a green oil (2.21 g,71 %). dH (400 MHz, CDCl3) 9.78 (t, J 1.6, 1H, CHO), 7.37-7.27 (m, 5H, ArH), 4.49 (s, 2H, PhCH2), 3.51 (t, 2H, J 6.0,BnOCH2), 2.55 (dt, J 7.1, 1.5, 2H, CH2CHO), 1.95 (q, J 13.2,7.1, 2H, CH2CH2CHO). dC (100 MHz, CDCl3) 202.3 (CHO), 138.3 (ArCquat), 128.4 (meta-ArC), 128.4 (para-ArC), 127.6(ortho-ArC), 73.0 (PhCH2), 69.2 (BnOCH2), 41.0 (CH2CHO),22.6 (CH2CH2CHO); spectroscopic data in accordance withliterature values. |
71% | With 1-methyl-1H-imidazole; [2,2]bipyridinyl; copper(I) tetrakis(acetonitrile) hexafluorophosphate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In acetonitrile at 20℃; | |
70% | With pyridinium chlorochromate | |
70% | With Dess-Martin periodane In dichloromethane at 17 - 25℃; for 4h; Inert atmosphere; | Intermediate 98a: 4-(Benzyloxy)butanal Intermediate 98a: 4-(Benzyloxy)butanal 1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (5.88 g, 13.90 mmol) was added to a stirred solution of 4-(benzyloxy)butan-1-ol (2.44 mL, 13.90 mmol) in DCM (50 mL) at RT under N2 for 4 hours. The mixture was partitioned between 1M NaOH solution and DCM, the organics separated washed with water, dried over MgSO4 and evaporated under reduced pressure. The residue was purified by flash silica chromatography, elution gradient 0 to 30% heptane in EtOAc. Pure fractions were evaporated to dryness to afford the title compound (1.74 g, 70%) as a colourless oil; 1H NMR (400 MHz, CDCl3, 30° C.) 1.89-2 (2H, m), 2.54 (2H, td), 3.50 (2H, t), 4.48 (2H, s), 7.26-7.37 (5H, m), 9.77 (1H, t). |
69% | With dmap; copper(I) tetrakis(acetonitrile) hexafluorophosphate; N,N'-di-tert-butylethylenediamine; oxygen In dichloromethane at 20℃; for 6h; Schlenk technique; Molecular sieve; Sealed tube; | |
68% | With anhydrous Sodium acetate; pyridinium chlorochromate In dichloromethane at 20℃; for 2h; | |
63% | With iodosylbenzene; ytterbium(III) nitrate In 1,2-dichloro-ethane at 80℃; for 5h; | |
58% | With pyridinium chlorochromate In dichloromethane at 20℃; for 3h; | |
56% | With piridinium dichromate; Celite In dichloromethane for 22h; | |
50% | With pyridinium chlorochromate In dichloromethane at 20℃; for 16h; | 1.28.1 Step 1 Into a 250-mL round-bottom flask, was placed 4-(benzyloxy)butan-1-ol (5.00 g, 27.74 mmol, 1.00 equiv), DCM (100 mL), and PCC (11.96 g, 55.47 mmol, 2.00 equiv). The mixture was stirred for 16 h at room temperature, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column and eluted with ethyl acetate/petroleum ether (1/10). This resulted in 2.5 g (50%) of 4- (benzyloxy)butanal was obtained as a colorless solid. LCMS (ES)[M+1]+ m/z: 179 |
50% | With pyridinium chlorochromate In dichloromethane at 20℃; for 16h; | 1.28.1 Step 1 Into a 250-mL round-bottom flask, was placed 4-(benzyloxy)butan-1-ol (5.00 g, 27.74 mmol, 1.00 equiv), DCM (100 mL), and PCC (11.96 g, 55.47 mmol, 2.00 equiv). The mixture was stirred for 16 h at room temperature, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column and eluted with ethyl acetate/petroleum ether (1/10). This resulted in 2.5 g (50%) of 4- (benzyloxy)butanal was obtained as a colorless solid. LCMS (ES)[M+1]+ m/z: 179 |
With Py*HClCrO3; anhydrous Sodium acetate In dichloromethane | ||
With pyridinium chlorochromate In dichloromethane for 0.5h; Ambient temperature; | ||
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane Yield given; | ||
With pyridinium chlorochromate | ||
With 4 A molecular sieve; pyridinium chlorochromate In dichloromethane for 1.5h; Ambient temperature; | ||
With 2,4,6-trimethylphenyl bromide; triphenylphosphine In water monomer; N,N-dimethyl-formamide; acetone at 120℃; for 9h; Yield given; | ||
With piridinium dichromate; 4 A molecular sieve In dichloromethane for 2h; Ambient temperature; | ||
With anhydrous Sodium acetate; pyridinium chlorochromate | ||
With pyridine-SO3 complex; dimethyl sulfoxide; triethylamine In dichloromethane for 2h; | ||
With oxalyl dichloride; dimethyl sulfoxide; triethylamine | ||
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 0℃; | ||
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; for 2.33333h; | ||
With piridinium dichromate In dichloromethane | ||
With pyridinium chloroformate; Celite In dichloromethane at 20℃; for 4h; | ||
With Celite; pyridinium chlorochromate In dichloromethane at 20℃; for 4h; | ||
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; | ||
Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 0.5h; Stage #2: With N-ethyl-N,N-diisopropylamine In dichloromethane at -78 - -60℃; for 0.5h; | ||
With pyridinium chlorochromate In dichloromethane | ||
With pyridine-SO3 complex; dimethyl sulfoxide; triethylamine In dichloromethane at 0 - 20℃; for 2h; | ||
With 2,2,6,6-tetramethyl-1-piperidinyloxy free radical | ||
With pyridinium chlorochromate | ||
With pyridinium chlorochromate In dichloromethane | ||
With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78 - 0℃; | ||
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -60 - 20℃; | ||
With pyridinium chlorochromate In dichloromethane | 15 EXAMPLE 15 36.6 g (170 mmol) of pyridinium chlorochromate are placed at room temperature in 120 ml of dichloromethane under N2, and a solution of 20.4 g (113 mmol) of 4-benzyloxybutanol in 20 ml of dichloromethane is added. The reaction mixture rapidly becomes dark and the reaction is slightly exothermic. The reaction mixture is stirred at room temperature for 31/2 hours. The supernatant dichloromethane phase is decanted off and concentrated by evaporation in a rotary evaporator. The residue is filtered over 100 g of silica gel. The product fractions are concentrated by evaporation in a rotary evaporator and distilled under a high vacuum over a 10 cm Vigreux column. 4-benzyloxybutanal is obtained, b.p.0.1 =72°-73°. | |
Stage #1: With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 0.916667h; Inert atmosphere; Stage #2: 4-benzyloxy-butan-1-ol With triethylamine In dichloromethane at -78 - 20℃; | ||
Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 0.5h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; for 0.5h; Inert atmosphere; | ||
With anhydrous Sodium acetate; pyridinium chlorochromate In dichloromethane for 3h; | ||
Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 1h; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; | ||
Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 1h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; | ||
Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 0.333333h; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; for 1.16667h; | (E)-Ethyl 6-(benzyloxy)-2-methylhex-2-enoate (9b): A flame-dried round-bottom flask was charged with a solution of oxalylchloride (3.8 mL, 43.1 mmol) in CH2Cl2 (45 mL) at -78 °C. The mixture was added to dimethylsulfoxide (6.1 mL, 87.1 mmol) at -78 °C. This mixture was stirred for 20 min,and then a solution of the alcohol (5.0 g, 27.7 mmol), prepared as described inthe preceding procedure, in CH2Cl2 (14 mL) was added.After 20 min, triethylamine (19.3 mL, 138.5 mmol) was added to the reactionmixture and stirred for 10 min. The resulting mixture was warmed to roomtemperature and stirred for 1 h. The reaction mixture was diluted with ether(30 mL), and water (30 mL) was added. The organic layer was separated, and theaqueous layer was extracted with ether (2 × 30 mL), and washed with saturatedaqueous NaHCO3 (15 mL) and saturated aqueous NaCl (15 mL). Theorganic solutions were combined, dried (Na2SO4), and concentratedto afford the desired crude aldehyde (4.90 g, 27.5 mmol, 99%) as a colorlessoil which was used in the next step without further purification. | |
With pyridinium chlorochromate In dichloromethane at 20℃; Molecular sieve; Inert atmosphere; | ||
With mesoporous silica; pyridinium chlorochromate In dichloromethane at 0 - 20℃; for 2h; | ||
With pyridinium chlorochromate In dichloromethane at 20℃; for 4h; | ||
Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 1.25h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; Inert atmosphere; | (E)-Ethyl 6-(benzyloxy)hex-2-enoate (20): DMSO (7.88 mL, 0.11 mol) was added at -78 oC to a solution of oxalyl chloride (7.24 mL, 0.08 mol) in CH2Cl2 (100 mL), and the resulting solution was stirred for 15 min. A solution of the monobenzylated alcohol 19 (10 g, 55.55 mmol) in CH2Cl2 (50 mL), was added drop wise at -78 oC over 30 min. After the solution had been stirred for an additional 30 min, Et3N (46.37 mL, 0.33 mol) was added and the reaction mixture was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was poured into ice cooled water and extracted with CH2Cl2. The organic layer was washed with brine, dried with Na2SO4, and concentrated under reduced pressure to give crude aldehyde (8.9 g) which was directly used for next step without further purification. To a stirred solution of aldehyde (8.9 g, 50.0 mmol) in C6H6 (100 mL), was added (ethoxycarbonylmethylene)triphenylphosphorane (19.2 g, 55.0 mmol) and the mixture was heated at reflux for 4 h. After completion of the reaction, solvent was removed in vacuo then purified by column chromatography to afford 20 (11.78 g, 85% over two steps) as a light yellow oil. | |
With sodium chlorine monoxide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; Potassium bicarbonate; potassium bromide In water monomer; ethyl acetate; toluene for 3.5h; Cooling with ice; | 154.1 Step 1 4-Benzyloxy-butylaldehyde 4-Benzyloxy-butan-1-ol (5.0 g), potassium bromide (0.66 g), and 2,2,6,6-tetramethylpiperidine 1-oxyl free radical (43.1 mg) were mixed in toluene (15 mL), ethyl acetate (15 mL), and water (3 mL). To the reaction solution were added dropwise a mixed solution of potassium hydrogen carbonate (5.55 g) in water (15 mL) and then 15 w/w/o aqueous sodium hypochlorite solution (16.5 mL) under ice cooling. The reaction solution was stirred under ice cooling for 1.5 hours. To the reaction solution was added 15 w/w % aqueous sodium hypochlorite solution (4 mL), and the reaction solution was stirred for additional 2 hours. The reaction solution was extracted with toluene. The organic layer was washed sequentially with water, a mixed solution of potassium iodide (73 mg) in 1M hydrochloric acid (5 mL), a mixed solution of sodium thiosulfate (2.3 g) and potassium carbonate (4.02 g) in water (8.3 mL), and aqueous saturated sodium chloride solution, and dried over magnesium sulfate. After removing magnesium sulfate on a filter, the filtrate was concentrated under reduced pressure to give the titled compound (4.08 g) as a crude product. (0850) 1H-NMR (400 MHz, CDCl3) 1.91-1.99 (m, 2H), 2.55 (td, J=7.05, 1.62 Hz, 2H), 3.51 (t, J=6.13 Hz, 2H), 4.49 (s, 2H), 7.15-7.37 (m, 5H), 9.79 (t, J=1.62 Hz, 1H) | |
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78℃; Inert atmosphere; | ||
Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 0.5h; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; | ||
With sodium chlorine monoxide; Sodium hydrogenocarbonate; potassium bromide In dichloromethane; water monomer for 0.5h; | 19 Example 19: 4-Benzyloxybutyraldehvde; A procedure is followed as described by Rychnovsky (Angew. Chem. Int. Ed. 2004, 43,2822-2826).To a stirred solution of 4-benzyloxy-butan-1-ol (50) (10.28 g, 57 mmol) in DCM (570 ml.) at 00C is added potassium bromide (1.36g, 1 1.4 mmol, in water 23 ml_), TEMPO (0.178 g, 1.14 mmol) and then a mixture of sodium hypochlorite (9.1 % available chlorine, 50 ml_, 80 mmol), water (64 ml.) and aqueous sodium bicarbonate solution (8%, 1 14 ml.) is added. The orange biphasic mixture is stirred vigorously until the orange colour fades (30 min). The phases are separated and the aqueous layer is extracted with DCM. The combined organics are dried (Na2SO4) and concentrated to yield an orange oil.H NMR (400 MHz, CDCI3) δH (ppm) 9.80 (1H, s, CHO), 7.38-7.29 (5H, m, Ar-H), 4.50 (2H, s, Ph-CH2O), 3.52 (2H, t, J 6 Hz), 2.56 (2H, dt, J 1.6 Hz, 7.1 Hz), 1.97 (2H, qu, J 7.1 Hz). | |
Stage #1: 4-benzyloxy-butan-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 1h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; for 1h; Inert atmosphere; | DMSO (9.8 mL, 138.8 mmol) was added at -78 °C to a solution of oxalyl chloride (9.7 mL, 111.0 mmol) in CH2Cl2 (100 mL), and the resulting solution was stirred for 15 min. A solution of the mono benzylated alcohol 18 (10 g, 55.5 mmol) in CH2Cl2(50 mL), was added drop wise at -78 °C over 30 min. After the solution had been stirred for an additional 30 min, Et3N (38.2 mL, 275.0 mmol) was added and the reaction mixture was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was poured into ice cooled water and extracted with CH2Cl2. The organic layer was washed with brine, dried with Na2SO4 and concentrated under reduced pressure to give crude aldehyde (8.9 g) which was directly used for next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In dichloromethane at 0 - 20℃; for 1h; | (E)-Ethyl6-(benzyloxy)-2-methylhex-2-enoate (6c) To a stirredsolution of ethyl-2-(triphenylphosphoranylidene)propionate (48.86 g, 13.466mmol) in CH2Cl2 (50 mL) was added aldehyde 6c (2.08 g, 11.222 mmol) at 0 °C andstirred at room temperature. The reaction was slightly exothermic and completein one hour. The solvent was removed under atmospheric pressure and the residuewas purified by silica gel column chromatography (EtOAc/hexanes, 1:19) toafford the ester 6c (2.30 g, 75%) asa colourless oil. 1H NMR (300 MHz, CDCl3)δ 7.34-7.19 (m, 5H), 6.71 (t, J = 7.5 Hz, 1H), 4.46 (s, 2H), 4.16 (q, J = 6.7 Hz, 2H), 3.45 (t, J = 6.0 Hz, 2H), 2.28 (q, J = 7.5 Hz, 2H), 1.82 (s, 3H), 1.74(t, J = 7.5 Hz, 2H),1.28 (t, J = 6.7 Hz, 3H);13C NMR (75 MHz, CDCl3) δ 168.1, 141.3, 138.4, 128.2,128.2, 127.5, 127.4, 72.9, 69.4, 60.3, 28.6, 25.3, 14.2, 12.2; IR (neat): nmax2932, 2860, 1710, 1648, 1451, 1366, 1266, 1096, 1028, 742, 699, 538 cm-1;ESI-MS (m/z): 285 (M+Na)+;HRMS (ESI): calcd for C16H22O3Na (M+Na)+,285.1466, found 285.1476. |
In tetrahydrofuran at 80℃; for 4h; | ||
11.021 g | In tetrahydrofuran at 80℃; for 4h; |
6.60 g | In toluene at 20 - 110℃; for 16.5h; | (E)-Ethyl 6-(benzyloxy)-2-methylhex-2-enoate (9b) General procedure: To a stirred solution ofethyl-2-(triphenylphosphoranylidene)propionate (8b) (15.0 g, 41.2 mmol) in toluene was added a solution of crudealdehyde (4.90 g, 27.5 mmol), prepared as described in the preceding procedure,in toluene (60 mL) at room temperature. Theresulting solution was stirred for 30 min at room temperature and then heatedup to 110 °C. After additional stirring for 16 h at 110 °C, the solution wascooled to room temperature. After stirring for 30 min, the reaction mixture wasconcentrated. The residue was purified by flash chromatography (hexane /EtOAc =5:1) to afford the desired ester 9b(6.60 g, 25.2 mmol, 91 % for two steps) as a colorless oil: IR (film) νmax 2938, 1709, 1649, 1603,1453, 1367, 1271, 1201, 1096, 1027 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.37-7.27 (m, 5H, -OCH2Ph), 6.76 (td, J = 1.2,7.4 Hz, 1 H, -CH2CHC(CH3)-),4.50 (s, 2 H, -OCH2Ph),4.19 (q, J = 7.2 Hz, 2 H, -C(O)OCH2CH3), 3.49 (t, J = 6.4 Hz, 2 H, -OCH2CH2-), 2.29 (q, J = 7.6 Hz, 2 H, -CH2CH2CH-), 1.84 (s, 3 H, -CHC(CH3)-), 1.77 (quintet, J = 6.4 Hz, 2 H, -OCH2CH2CH2-), 1.29 (t, J = 7.2 Hz, 3 H, -C(O)OCH2CH3); 13C NMR (100 MHz, CDCl3) δ 168.0, 141.3, 138.3, 128.2, 128.1,127.4, 127.4, 72.8, 69.4, 60.2, 28.5, 25.2, 14.1, 12.2; HRMS (FAB) calcd. for C16H23O3[M + H]+ 263.1647, found 263.1646 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 93% 2: 5% | With water; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dimethyl sulfoxide at 20℃; for 0.5h; | |
1: 18% 2: 73.9% | With water; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dimethyl sulfoxide at 20℃; for 0.75h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 37% 2: 30% | Stage #1: N-(t-butoxycarbonyl)-4-chloroaniline With tert.-butyl lithium In tetrahydrofuran at -78 - 0℃; for 2.5h; Stage #2: 4-benzyloxybutanal In tetrahydrofuran at -78℃; for 2h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: (3-ethoxycarbonylpropyl)triphenylphosphonium bromide With sodium hexamethyldisilazane In tetrahydrofuran at 0℃; for 0.333333h; Stage #2: 4-benzyloxybutanal In tetrahydrofuran at -78℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With n-butyllithium; iodine; 1,1,1,3,3,3-hexamethyl-disilazane In tetrahydrofuran at -78℃; for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | A solution of 186.000 mmol of N,N-dimethyl-2-(tert-butyldimethylsilanyl)imidazole-1 -sulphon- amide [129378-52-5] in 1.35 I of tetrahydrofuran is cooled to internal temperature approx. -70C by means of an external ethanol/dry ice bath. A solution of 203.000 mmol of sec-butyl- lithium (156 ml, 1 .3 M in cyclohexane) is added dropwise within 45 minutes. The reaction mixture is stirred at this temperature for a further 30 minutes. A solution of 169.000 mmol of 4-benzyloxybutyraldehyde in 150 ml of tetrahydrofuran is then added dropwise with stirring within 30 minutes. The mixture is stirred at -70C for a further hour, the cold bath is removed and the reaction mixture is quenched at 0C cautiously with 200 ml of aqueous saturated ammonium chloride solution, followed by 200 ml of water. The organic phase is removed and the aqueous phase is then extracted with tert-butyl methyl ether (2 x 200 ml). The combined organic phases are washed with brine (1 I), dried over magnesium sulphate and concentrated by evaporation. 141.1 1 1 mmol (83% based on the aldehyde) of the title compound are obtained from the residue as a brownish oil via flash chromatography (SiO2 6OF, heptane/ethyl acetate = 1 .5:1 ). Rf = 0.68 (heptane/ethyl acetate = 1 :2), Rt = 7.96. | |
83% | A solution of 186.000 mmol of N,N-dimethyl-2-(tert-butyldimethylsilanyl)imidazole-1-sulphonamide [129378-52-5] in 1.35 l of tetrahydrofuran is cooled to internal temperature approx. -70 C. by means of an external ethanol/dry ice bath. A solution of 203.000 mmol of sec-butyllithium (156 ml, 1.3 M in cyclohexane) is added dropwise within 45 minutes. The reaction mixture is stirred at this temperature for a further 30 minutes. A solution of 169.000 mmol of 4-benzyloxybutyraldehyde in 150 ml of tetrahydrofuran is then added dropwise with stirring within 30 minutes. The mixture is stirred at -70 C. for a further hour, the cold bath is removed and the reaction mixture is quenched at 0 C. cautiously with 200 ml of aqueous saturated ammonium chloride solution, followed by 200 ml of water. The organic phase is removed and the aqueous phase is then extracted with tert-butyl methyl ether (2×200 ml). The combined organic phases are washed with brine (1 l), dried over magnesium sulphate and concentrated by evaporation. 141.111 mmol (83% based on the aldehyde) of the title compound are obtained from the residue as a brownish oil via flash chromatography (SiO2 60F, heptane/ethyl acetate=1.5:1). Rf=0.68 (heptane/ethyl acetate=1:2), Rt=7.96. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With caesium carbonate In 1,4-dioxane at 80℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With caesium carbonate In 1,4-dioxane at 80℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | Stage #1: 2-Iodobenzoic acid With sodium azide; benzyl chloroformate; sodium t-butanolate In N,N-dimethyl-formamide at 75℃; for 5h; Stage #2: 4-benzyloxybutanal With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 120℃; for 16h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | at 0 - 23℃; Inert atmosphere; | |
85% | With magnesium sulfate In dichloromethane at 20℃; for 12h; | |
78% | With magnesium sulfate In dichloromethane at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In dichloromethane at -78 - 20℃; Molecular sieve; | 3 A solution of R-BINOL (1.02 g, 3.58 mmol) in CH2Cl2 (30 ml) was treated with 3 molecular sieves (6.0 g) and Ti(OiPr)4 (1.06 ml, 3.58 mmol) and refluxed for 1 h. The resulting mixture was cooled to 20° C., treated with 4-benzyloxybutyraldehyde 35 (3.19 g, 17.9 mmol) in 10 ml CH2Cl2, cooled further to -78° C. and treated with allyltributylstannane (6.66 ml, 21.5 mmol). The reaction mixture was stirred for 3 days at -20° C., treated with saturated aqueous solution of Na2CO3 (50 ml) and CH2Cl2 (50 ml). The stirring continued for 2 h. The reaction mixture was filtered. The layers were separated. The aqueous layer was extracted with CH2Cl2 (2×50 ml). Combined organic layers were dried with MgSO4, filtered and concentrated. The product was purified by flash column chromatography on silica gel (elution with 4:1 hexane:EtOAc) followed by bulb-to-bulb distillation to give the expected alcohol (2.51 g, 83% yield) in 91% ee (Mosher ester analysis). |
83% | Stage #1: 4-benzyloxybutanal With titanium(IV) isopropylate; (S)-[1,1']-binaphthalenyl-2,2'-diol In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Molecular sieve; Stage #2: allyltributylstanane In dichloromethane at -78 - -20℃; for 12h; Inert atmosphere; Molecular sieve; enantioselective reaction; | 3.3.3. General Procedure for Synthesis of (R)-7-(benzyloxy)hept-1-en-4-ol (15) and (S)-7-(benzyloxy)hept-1-en-4-ol (ent-15), with Alcohol 15 as an Example. General procedure: Under Ar atmosphere, (S)-BINOL (52 mg, 0.2 mmol) and Ti(OiPr)4 (45 mg, 0.2 mmol) were addedto a solution of dried 4 Å molecular sieves (2.2 g) in CH2Cl2 (20 mL). The reaction mixture was heatedat reflux for 1 h, and then allowed to cool to room temperature. A solution of aldehyde 16 (356 mg, 2mmol) in CH2Cl2 (15 mL) was added to the reaction mixture. After stirring for 0.5 h at roomtemperature, the solution was cooled to -78 °C and allyltributyltin (993 mg, 3 mmol) was addeddropwise. The reaction mixture was stirred for an additional 20 min at -78 °C, then kept at -20 °C.After 12 h, the reaction mixture was filtered through a pad of celite into a 200 mL flask that containeda stirred sat. aq. NaHCO3 solution (50 mL); the resulting reaction mixture was stirred for 1 h. Then,the layers were separated and the aqueous layer was extracted with CH2Cl2 (3 × 50 mL). The combinedorganic extracts were dried with MgSO4; subsequent removal of all volatiles under reduced pressureand column chromatography of the residue on silica gel (petroleum ether/EtOAc = 20/1) affordedhomoallylic alcohol 15 (729.7 mg, 83% yield) as colorless oil. Data for 15: [α]D 20 +4.14 (c 3.85 in CH2Cl2); HPLC analysis: 92.6% ee [Daicel CHIRALPAK OD-Hcolumn, 20 °C, 220 nm, hexane/i-PrOH = 95:5, 1 mL/min, 20.8 min (major), 23.9 min (minor)];νmax/cm-1: 3401 (s), 3068 (w), 2924 (s), 1679 (w), 1453 (m), 1096 (s), 1021 (m), 697 (m); 1H-NMR (300MHz, CDCl3) δ 7.39-7.23 (m, 5H), 5.93-5.75 (m, 1H), 5.15-5.10 (m, 1H), 5.08 (t, J = 1.2 Hz, 1H), 4.50 (s,2H), 3.64 (tt, J = 8.1, 4.5 Hz, 1H), 3.50 (t, J = 6.0 Hz, 2H), 2.52 (br, 1H), 2.26-2.15 (m, 2H), 1.77-1.60 (m,3H), 1.54-1.45 (m, 1H); 13C-NMR (75 MHz, CDCl3) δ 138.3, 135.1, 128.4, 127.7, 127.7, 117.7, 73.0, 70.6,70.5, 42.0, 34.0, 26.2; HRMS(ESI) calcd for C14H21O2+ [M + H]+ 243.13555, found 243.13564. |
80% | Stage #1: 4-benzyloxybutanal With titanium(IV) isopropylate; (S)-[1,1']-binaphthalenyl-2,2'-diol In dichloromethane for 1.16667h; Molecular sieve; Reflux; Stage #2: allyltributylstanane In dichloromethane at -78 - -20℃; for 48h; Molecular sieve; | (R)-7-(Benzyloxy)hept-1-en-4-ol (10): A mixture of (S)-BINOL (635 mg, 2.22 mmol) and Ti(OiPr)4 (0.65 mL, 2.22 mmol) in CH2Cl2(20 mL) in the presence of 4 A° molecular sieves (4.0 g) was stirred under reflux for 1 h. After 1 h, the mixture was cooled to room temperature, 4-benzyloxybutyraldehyde 9 (2.0 g, 11.11 mmol) was added and the resulting mixture was stirred for 10 min. Then, the reaction was cooled to -78 °C and allyltributyl stannane (4.1 mL, 13.33 mmol) was added and stirring continued at -20 °C for 48 h. The reaction was quenched with saturated aqueous NH4Cl solution (30 mL) and extracted with CH2Cl2 (2 x 50 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na2SO4,evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexanes/EtOAc, 7:3) to afford 10 (1.96 g, 80%) as colorless liquid. Rf = 0.1 (20% EtOAc in hexanes). [α]D20 = +6.2 (c= 1.1, CHCl3). 1H NMR (CDCl3, 300 MHz): δ7.27-7.39 (m, 5H), 5.76-5.91 (m,1H), 5.07-5.16 (m, 2H), 4.52 (s, 2H), 3.62-3.70 (m, 1H), 3.52 (t, J = 6.0 Hz, 2H), 2.13-2.33 (m, 3H),1.60-1.80 (m, 3H), 1.42-1.56 (m, 1H) ppm. 13C NMR (CDCl3,75 MHz): δ 138.1, 134.9, 128.3, 127.6, 127.5, 117.7, 72.9, 70.5, 70.4, 41.9, 33.9,26.1 ppm. IR: νmax 3386,2926, 1451, 1275, 1098, 737 cm-1. MS (ESI): m/z = 243[M+Na]+. HRMS (ESI): m/z [M+Na]+ calcd forC14H20NaO2 243.1356; found 243.1363. |
74% | Stage #1: 4-benzyloxybutanal With titanium(IV) isopropylate; (S)-[1,1']-binaphthalenyl-2,2'-diol In dichloromethane at 20℃; Inert atmosphere; Molecular sieve; Stage #2: allyltributylstanane In dichloromethane at -78 - -20℃; Inert atmosphere; Molecular sieve; Stage #3: With sodium hydrogencarbonate In dichloromethane; water at -78℃; | (4R)-7-Benzyloxy-1-heptene-4-ol (+)-13 To a solution of (S)-BINOL (369.8 mg, 1.292 mmol) and 4A MS (2.30 g) in CH2Cl2 (36 mL) was added Ti(Oi-Pr)4 (0.380 mL, 1.29 mmol), and the resultant mixture was heated to reflux for 1 h. A solution of aldehyde 12 (2.30 g, 12.9 mmol) in CH2Cl2 (7 mL) was added to the reaction mixture at room temperature. The resultant mixture was cooled to -78 °C and then treated with allyl tri-n-butylstannane (4.80 mL, 15.5 mmol). After being stirred at -20 °C for 84 h, the reaction mixture was cooled to -78 °C and quenched with saturated aqueous NaHCO3 solution. The resultant mixture was allowed to warm to room temperature. Insoluble materials were filtered off, and the filtrate was extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification of the residue by flash chromatography on silica gel (3 to 20% EtOAc/hexanes) gave the title compound (+)-13 (2.10 g, 74%) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: (S)-3-propanoyl-4-benzyl-1,3-thiazolidine-2-thione With titanium tetrachloride In dichloromethane at -15℃; for 0.25h; Inert atmosphere; Stage #2: With (-)-sparteine In dichloromethane at -15℃; for 0.5h; Inert atmosphere; Stage #3: 4-benzyloxybutanal In dichloromethane at -15℃; for 1h; Inert atmosphere; | |
90% | Stage #1: (S)-3-propanoyl-4-benzyl-1,3-thiazolidine-2-thione With titanium tetrachloride In dichloromethane at -15℃; Stage #2: With (-)-sparteine In dichloromethane at -15℃; for 0.5h; Stage #3: 4-benzyloxybutanal In dichloromethane at -15℃; for 1h; | (2R,3S)-1-((S)-4-Benzyl-2-thioxothiazolidin-3-yl)-6-(benzyloxy)-3-hydroxy-2-methylhexan-1-one(10). To a dry 1000 mL round-bottomflask, under nitrogen, was added N-acetylthiazolidinethione (14.7g, 55.471 mmol) in 250 mL CH2Cl2. The solution was cooledto -15 °C and titanium tetrachloride (30.63 mL, 61.018 mmol, 2M solution in CH2Cl2)was added dropwise. The thick suspension was stirred for 15 min and then(-)-sparteine was added (11.75 mL, 55.471 mmol). The resulting dark redsolution was stirred for 30 min at -15 °C and then aldehyde 6b (11.75 g, 65.929 mmol) was added in60 mL CH2Cl2. The reaction mixture was stirred for 1 h at-15 °C and the reaction was quenched with saturated NH4Cl (100 mL).The layers were separated and the aqueous layer was extracted with CH2Cl2(3 x 150 mL). The combined organic layers were dried over anhydrous Na2SO4and concentrated under reduced pressure. The crude product was purified bysilica gel column chromatography EtOAc/hexanes, 2:8) to afford the alcohol 10 (26.30 g, 90%) as yellow viscousoil. [α]25D +71.8 (c 1.1, CHCl3). 1HNMR (500 MHz, CDCl3) δ7.37-7.15(m, 10H), 5.38-5.32 (m, 1H), 4.65 (dq, J = 2.7, 6.5 Hz, 1H), 4.49 (s, 2H),4.05-4.01 (brs, 1H), 3.50 (t, J= 6.5 Hz, 2H), 3.33 (dd, J= 3.7, 11.1 Hz, 1H), 3.22 (dd, J = 3.7, 13.0 Hz, 1H), 3.00 (dd, J = 10.5, 13.0 Hz, 1H), 2.97-2.85 (m, 2H), 1.85-1.50 (m, 4H),1.19 (d, J = 6.5 Hz,3H); 13C NMR (75 MHz, CDCl3) δ 201.4, 178.0, 138.2,136.3, 129.3, 129.1, 128.9, 128.8, 128.2, 127.5, 127.4, 127.4, 127.1, 72.8,70.8, 70.1, 68.8, 42.8, 40.0, 36.8, 31.7, 26.2, 10.5; IR (neat): nmax3446, 3062, 3028, 2937, 2854, 1688, 1493, 1343, 1294, 1259, 1190, 1160, 1032,963, 744, 700, 659 cm-1; ESI-MS (m/z):466 (M+Na)+; HRMS (ESI): calcd for C24H29NO3S2Na(M+Na)+, 466.1486, found 466.1500. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 4-benzyloxybutanal; (1R,2S)-1-Amino-2-indanol With sodium sulfate In dichloromethane for 12h; Inert atmosphere; Stage #2: (E/Z)-crotyl bromide With indium In methanol at 20℃; for 3h; Inert atmosphere; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: 4-benzyloxybutanal With titanium(IV) isopropylate; (R)-1,1'-Bi-2-naphthol In dichloromethane at 20℃; for 0.5h; Molecular sieve; Inert atmosphere; Stage #2: allyltributylstanane In dichloromethane at -78 - -20℃; for 24h; Molecular sieve; Inert atmosphere; enantioselective reaction; | (S)-7-(benzyloxy)hept-1-en-4-ol To the stirred solution of oven-dried 4-Å molecular sieves (25 g) in CH2Cl2(133 mL) under N2 atmosphere, was added (R)-BINOL (1.6 g, 5.6 mmol) a 1.0 M solution of Ti(OiPr)4 (1.6mL, 5.6 mmol) in CH2Cl2. The reaction mixture was heated atreflux for a period of 1 h, and then allowed to cool to room temperature.Aldehyde 9 (10 g, 56.1 mmol) in CH2Cl2(40 mL), was added to the reaction mixture. After the mixture stirred for0.5 h at room temperature, cooled to -78 °C, allyltributyltin (20.6g, 62.3 mmol) was slowly added. The reaction mixture as stirredfor an additional 10 min at -78 °C, then kept in a -20 °C. After 24 h, thereaction mixture was filtered through a pad of celite in to a 500 mL flask thatcontained a stirring saturated aqueous NaHCO3 solution (50 mL) andthe resulting mixture was stirred for 1 h, then the layers were separated. Theaqueous layer was extracted with CH2Cl2 (2×40 mL). Thecombined organic layers were washed with brine (40 mL), dried with Na2SO4,filtered, and concentrated under reduced pressure to give the crude product.The crude residue was purified by column chromatography (5% ethyl acetate inhexanes) to give (S)-7-(benzyloxy)hept-1-en-4-ol10 as a colourless oil. Yield: 10.6g (86%); [α]D25 = -7.4 (c 1, CHCl3);chiral HPLC analysis (Chiralpak AD-H column, IPA:n-Hexane, 05:95, 0.5 mL/min,220 nm) retention time 15.620 (1.00%) and 19.023 (99.00%) forchiral alcohol. IR (CHCl3, cm-1) :3363, 3016, 1640, 1216, 771, 668; 1HNMR (200 MHz, CDCl3) d 7.31 (s, 5H), 5.71-5.92 (m, 1H), 5.14 (m, J= 15.0 Hz, 2H ), 4.5 (s, 2H ), 3.64 (br, s, 1H) 3.50 (t, J = 6.0 Hz, 2H), 2.43 (br. s, 1H),2.09-2.25 (m, 2H) 1.38-1.76 (m, 4H); 13CNMR (50 MHz,CDCl3) d:138.1, 135.0, 128.3, 127.5, 117.6, 72.9, 70.3, 42.0, 34.0, 25.9; HRMS calcd for C14H20O2Na (M+H )+ 243.1356.found 243.1354 |
86% | Stage #1: 4-benzyloxybutanal With titanium(IV) isopropylate; (R)-1,1'-Bi-2-naphthol In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Molecular sieve; Stage #2: allyltributylstanane In dichloromethane at -78 - -20℃; for 12h; Inert atmosphere; Molecular sieve; enantioselective reaction; | 3.3.3. General Procedure for Synthesis of (R)-7-(benzyloxy)hept-1-en-4-ol (15) and (S)-7-(benzyloxy)hept-1-en-4-ol (ent-15), with Alcohol 15 as an Example. General procedure: Under Ar atmosphere, (S)-BINOL (52 mg, 0.2 mmol) and Ti(OiPr)4 (45 mg, 0.2 mmol) were addedto a solution of dried 4 Å molecular sieves (2.2 g) in CH2Cl2 (20 mL). The reaction mixture was heatedat reflux for 1 h, and then allowed to cool to room temperature. A solution of aldehyde 16 (356 mg, 2mmol) in CH2Cl2 (15 mL) was added to the reaction mixture. After stirring for 0.5 h at roomtemperature, the solution was cooled to -78 °C and allyltributyltin (993 mg, 3 mmol) was addeddropwise. The reaction mixture was stirred for an additional 20 min at -78 °C, then kept at -20 °C.After 12 h, the reaction mixture was filtered through a pad of celite into a 200 mL flask that containeda stirred sat. aq. NaHCO3 solution (50 mL); the resulting reaction mixture was stirred for 1 h. Then,the layers were separated and the aqueous layer was extracted with CH2Cl2 (3 × 50 mL). The combinedorganic extracts were dried with MgSO4; subsequent removal of all volatiles under reduced pressureand column chromatography of the residue on silica gel (petroleum ether/EtOAc = 20/1) affordedhomoallylic alcohol 15 (729.7 mg, 83% yield) as colorless oil. |
76% | With titanium(IV) isopropylate; (R)-1,1'-Bi-2-naphthol; titanium tetrachloride; silver(l) oxide In dichloromethane at -15 - 0℃; for 4h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With ester of 3,5-di-tert-butyl-4-hydroxyphenylpropionic acid and pentaerythritol; <i>L</i>-proline In dimethyl sulfoxide at 40℃; for 4h; Sonication; | General procedure for the preparation of β,γ-unsaturated α-nitrosulfones 4 General procedure: To a solution of phenylsulfonylnitromethane (1) (402 mg, 2.00 mmol) in DMSO (2.0 mL) were added at room temperature aldehyde 2 (2.00 mmol) and proline (12 mg, 0.10 mmol). If necessary, pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxy-hydrocinnamate) (6 mg, 0.005 mmol) was additionally added. The reaction ask was placed in a sonicator for 2 h. Then, aldehyde 2 (0.60 mmol) was added again to the reaction mixture, which was then placed in the sonicator for further 2 h. The mixture was diluted with ether (20 mL) and an aqueous 0.1 N HCl solution (20 mL) and extracted with ether (3 x 20 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated on a rotary evaporator under reduced pressure. The resulting crude oil was purified by silica gel column chromatography to afford 4 in 61e88% yields. The yields were calculated based on the amount of phenylsulfonylnitromethane (1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With 1,4-diaza-bicyclo[2.2.2]octane In neat (no solvent) at 20 - 40℃; | 2-(2'-Benzyloxyethyl)-4H-1,3-benzdioxin-4-one (3a) General procedure: This reaction was performed with a mixture DABCO (1.1g, 10 mmol), (2.15 g) phenyl salicylate and (1.518 g) of 3-benzyloxypropionaldehyde without solvent and was warmed to 40oC during 12 min then it continued during overnight at normal warmth condition where suspension formed which was extracted by EtOAc and was washed thoroughly with 30 mL 2% NaOH solution two times and aqua (30 mL x 2) and passed through drying agent. The crude compound was achieved after removal of organic solvent which made pure by chromatography (ca. 200 g) taking hexane/EtOAc (98:2, v/v) as solvent mixture to yield 3a clear liquid form (880 mg, 68%). |
Tags: 5470-84-8 synthesis path| 5470-84-8 SDS| 5470-84-8 COA| 5470-84-8 purity| 5470-84-8 application| 5470-84-8 NMR| 5470-84-8 COA| 5470-84-8 structure
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Code | Phrase |
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P378 | |
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P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
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Storage | |
Code | Phrase |
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P402 | Store in a dry place. |
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Disposal | |
Code | Phrase |
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Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
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H242 | Heating may cause a fire |
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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 |
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H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
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Health hazards | |
Code | Phrase |
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H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
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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 |
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H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
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H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
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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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