Structure of 4728-12-5
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CAS No. : | 4728-12-5 |
Formula : | C7H14O3 |
M.W : | 146.18 |
SMILES Code : | OCC1COC(C)(C)OC1 |
MDL No. : | MFCD04119722 |
InChI Key : | BTAUZIVCHJIXAX-UHFFFAOYSA-N |
Pubchem ID : | 3584869 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 37.02 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.69 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.83 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.01 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.38 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.09 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.68 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.67 |
Solubility | 31.0 mg/ml ; 0.212 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.35 |
Solubility | 64.8 mg/ml ; 0.443 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.81 |
Solubility | 22.6 mg/ml ; 0.155 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-7.2 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.8 |
* 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 1H-imidazole; carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 4h;Cooling with ice; | j0363] 2,2-Dimethyl-5-(hydroxymethyl)-1 ,3-dioxane (3a) (1.00 g) was dissolved in 22.8 mE of dichloromethane (MDC), and 700.0 mg of imidazole and 2.72 g of carbon tetrabromide were added thereto. After ice-cooling, 2.15 g of triphenylphosphine was thrther added, and the mixture was stirred at room temperature for 4 hours. Dichloromethane was distilled off under reduced pressure, and the resulting product was purified with silica gel chromatography (n-hexane:ethyl acetate=5: 1) to quantitatively obtain 1.60 g of 2,2-dimethyl-5-bromomethyl- 1 ,3-dioxane (Sb). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With pyridinium chlorochromate; In dichloromethane; at 20℃; for 8h; | To a stirring solution of 18.5 (731 mg , 5 mmoL) in DCM (20 mL) was added PCC (2.15 g, 10 mmol ) and the reaction mixture was stirred at r.t for 8 hours . The reaction was filtered, and the filtrate was washed with DCM . The combined organic layers were dried over Nu02·3Omicron and concentrated under reduced pressure to give a crude, which was purified by flash chromatography (silica gel/Et20) to give 18.6 (450 mg, 60percent) as a colorless oil. |
Example 4 2,2-dimethyl-l ,3-dioxane-5-carbaldehyde4-1 4-2Under N2 atmosphere, oxalyl chloride (1.4 eq.) was dissolved in DCM then cooled to -78° C. Dropwise, DMSO (2.2 eq.) was added. This solution was stirred for about 10 minutes, then triol 3-2 (1 eq.) was dissolved in more DCM for a total concentration of 0.2 M. After reacting for 5 minutes, TEA (5 eq.) was added. This mixture stirred for 10 minutes at -78° C, then for another 10 minutes at room temperature. This reaction was best monitored by TLC using a 1 : 1 ratio of hexane to ethyl acetate as the developing solvent and visualizing the results with CAM stain. The reaction mixture was used without further workup. | ||
Example 18; 2,2-dimethyl-l,3-dioxane-5-carbaldehyde; 18-1 18-2 <n="77"/>Under N2 atmosphere, oxalyl chloride (1.4 eq.) was dissolved in DCM then cooled to -78° C. Dropwise, DMSO (2.2 eq.) was added. This solution was stirred for about 10 minutes, then 18-1 (1 eq.) was dissolved in more DCM for a total concentration of 0.2 M. After reacting for 5 minutes, TEA (5 eq.) was added. This mixture stirred for 10 minutes at -78° C, then for another 10 minutes at room temperature. This reaction was best monitored by TLC using a 1 : 1 ratio of hexane to ethyl acetate as the developing solvent and visualizing the results with CAM stain. The reaction mixture containing 18-2 was used without further workup. |
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 2h; | Example 492-Nitro-6-f4-(4-trifluoromethoxy-phenyl)-piperazin-1-ylmethyl1-6,7-dihvdro-5H-imidazof2,1- b1H .31oxazine (53)Pyridinium chlorochromate (10.54 g, 48.9 mmol) is dissolved in dichloromethane (100 ml) and celite (10 g) is added and the suspension is stirred for 30 minutes. A solution of (2,2- dimethyl-1 ,3-dioxan-5-y.)rpiethanol (5 g, 34.2 mmol) in dry dichloromethane is added drop wise to the reaction mixture and stirred for 2h at room temperature. The reaction mixture is diluted with diethyl ether (80 ml), stirred for 10 minutes, filtered through celite, washed several times with ether and the solvent is removed in vacuo to give crude 2,2-dimethyl- [1,3]dioxane-5-carbaldehyde, which is used in the next step without further purification. | |
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 2h; | [000824] To a stirred suspension of pyridinium chlorochromate ( 1.1 g) and diatomaceous earth (10 g) in dichloromethane (10 mL) was added (2,2-dimethyl- 1, 3 -dioxan-5-yl)methanol (0.5 g) as a solution in dichloromethane (3 mL) dropwise. The mixture was stirred at room temperature for 2 hours. The suspension was filtered through diatomaceous earth and washed with ethyl acetate. The crude product was filtered through silica gel and concentrated to give the title compound. NMR (501 MHz, chloroform- ) delta 9.89 (s, 1H), 4.28 - 4.17 (m, 4H), 2.42 - 2.32 (m, 1H), 1.49 (s, 3H), 1.39 (s, 3H). MS (ESI) m/e 305.9 (2M+NH4)+. | |
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 2h; | To a stirred suspension of pyridinium chlorochromate (1.1 g) and diatomaceous earth (10 g) in dichloromethane (10 mL) was added (2,2-dimethyl-1,3-dioxan-5-yl)methanol (0.5 g) as a solution in dichloromethane (3 mL) dropwise. The mixture was stirred at room temperature for 2 hours. The suspension was filtered through diatomaceous earth and washed with ethyl acetate. The crude product was filtered through silica gel and concentrated to give the title compound. 1H NMR (501 MHz, chloroform-d) delta ppm 9.89 (s, 1H), 4.28? 4.17 (m, 4H), 2.42? 2.32 (m, 1H), 1.49 (s, 3H), 1.39 (s, 3H). MS (ESI) m/e 305.9 (2M+NH4)+. | |
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 2h; | To a stirred suspension of pyridinium chlorochromate (1.1 g) and diatomaceous earth (10 g) in dichloromethane (10 mL) was added (2,2-dimethyl-1,3-dioxan-5-yl)methanol (0.5 g) as a solution in dichloromethane (3 mL) dropwise. The mixture was stirred at room temperature for 2 hours. The suspension was filtered through diatomaceous earth and washed with ethyl acetate. The crude product was filtered through silica gel and concentrated to give the title compound. 1H NMR (501 MHz, chloroform-d) delta 9.89 (s, 1H), 4.28-4.17 (m, 4H), 2.42-2.32 (m, 1H), 1.49 (s, 3H), 1.39 (s, 3H). MS (ESI) m/e 305.9 (2M+NH4)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With lithium aluminium tetrahydride; In diethyl ether; at 20℃; for 3h;Inert atmosphere; | To a suspension of LiAihh (0.50 g . 13.2 mmol) in Epsilon2upsilon (30 ml) was added a solution of 18.4 (2.0? g . 1 1 mmoL) in E0 (30 ml.) dropwise under argon. The reaction mixture was stirred at r.t for 3 hr. The reaction was quenched with water (0.9 roU, filtered, and the filtrate was washed with E0 . The combined organic layers were dried and concentrated under reduced pressure to give 18.5 ( 1.56 g, 96percent) as a colorless oil. 1 H MR (400 MHz, DMSO~c delta 4.52 (i J=5.2H , 1 H), 3.81 (q, 2H), 3.60 (q, 2H), 3.38 (q, 2H). 1.70 (m, 1H), 1.29 (, 6H). |
76% | A solution of 2,2-dimethyl-[1,3]dioxane-5-carboxylic acid ethyl ester (7.03 g, 37.35 mmol) in tetrahydrofuran (20 ml) was added dropwise to a cooled to 0° C. suspension of lithium aluminum hydride (1.8 g, 48.55 mmol) in tetrahydrofuran (20 ml). The reaction was stirred at 0° C. for 20 min and at 25° C. for 2 h. After such time, ethyl acetate (1 ml) and a few crystals of sodium sulphate decahydrate were added with caution. After stirring at 25° C. for 1 h saturated sodium chloride solution was added and the product extracted with ethyl acetate (3.x.100 ml). The organics were washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo to afford (2,2-dimethyl-[1,3]dioxan-5-yl)-methanol (4.09 g, 76percent) as a clear oil: 1H NMR (300 MHz, CDCl3) delta ppm 1.39 (s, 3 H, CH3), 1.44 (s, 3 H, CH3), 1.79-1.90 (m, 1 H, CH), 2.15-2.26 (brs, 1 H, OH), 3.69-3.81 (m, 2 H, 2.x.OCH of 2.x.OCH2), 3.74 (d, J=6.8 Hz, 2 H, OCH2), 3.96-4.05 (m, 2 H, 2.x.OCH of 2.x.OCH2). | |
75.2% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2.33333h;Inert atmosphere; | Under nitrogen, to a solution of LiAlH4 (1.39 g, 36.58 mmol) in THF (40 mL) which was cooled to 0° C., compound Ij?-1 (5.29 g, 28.0 mmol) (according to the synthesis procedure in the patent WO 2008/0021032) was added dropwise. The mixture was stirred for 20 minutes at 0° C. and 2 hours at room temperature. When the reaction finished, the mixture was diluted with Et2O (30 mL). With an ice bath, H2O (0.14 mL) was added dropwise to the mixture, followed with NaOH solution (15percent, 0.14 mL) and H2O (0.42 mL) in sequence. After the mixture was stirred for 20 minutes at room temperature, appropriate amount of MgSO4 was added to it and then another 20 minutes for stirring proceeded. After filtration, the filtrate was concentrated under vacuum to afford compound Ii?-1 (3.1 g, 75.2percent). [0138] 1HNMR (500MHz, CDCl3) delta: 3.93-3.96 (m, 2H), 3.65-3.72 (m, 4H), 1.73-1.79 (m, 1H), 1.35(d, J=25.0 HZ, 6H). |
75.2% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2.33333h;Inert atmosphere; | Example 7: Preparation of compound Ii"-1: [0094] Under nitrogen, to a solution of LiAlH4 (1.39 g, 36.58 mmol) in THF (40 mL) which was cooled to 0°C, compoundIj"-1 (5.29 g, 28.0 mmol) (according to the synthesis procedure in the patent WO 2008/0021032) was added dropwise.The mixture was stirred for 20 minutes at 0°C and 2 hours at room temperature. When the reaction finished, the mixturewas diluted with Et2O (30 mL). With an ice bath, H2O (0.14 mL) was added dropwise to the mixture, followed with NaOHsolution (15percent, 0.14 mL) and H2O (0.42 mL) in sequence. After the mixture was stirred for 20 minutes at room temperature,appropriate amount of MgSO4 was added to it and then another 20 minutes for stirring proceeded. After filtration, thefiltrate was concentrated under vacuum to afford compound Ii"-1 (3.1 g, 75.2percent).1HNMR (500MHz, CDCl3) delta: 3.93-3.96 (m, 2H), 3.65-3.72 (m, 4H), 1.73-1.79 (m, 1H), 1.35 (d, J=25.0HZ, 6H). |
58% | With lithium aluminium tetrahydride; In tetrahydrofuran; for 2h;Inert atmosphere; Reflux; | LiAlH4 (60 g, 1.58 mol) was suspended in dry THF (500 mL) under inert atmosphere. The solution of 3 (188 g,1 mol) in THF (600 mL) was added dropwise and the mixture was refluxed for 2 hours. The mixture was quenched by 6M NaOH solution upon cooling and filtered; the precipitate was washed by ethyl acetate (300 mL). The solvents were evaporated and the residual oil was distilled yielding S3 (85 g, 58percent) as colorless liquid 1. 1H NMR (700 MHz, CDCl3, 300K): delta = 4.02 (dd, J = 4.3 Hz, 12.2 Hz, 2 H), 3.78 (dd, J = 5.8 Hz,12.2 Hz, 2 H), 3.76 (dd, J = 5.1 Hz, 6.6 Hz, 2 H), 1.83-1.87 (m, 1H), 1.66 (t, J = 5.1 Hz, 1 H),1.45 (s, 3 H), 1.41 (s, 3 H). |
With sodium hydroxide; In water; | EXAMPLE 4 2,2-Dimethyl-5-Hydroxymethyl-1,3-Dioxane Lithium aluminum hydride (80 g) is stirred in ether (2000 ml) while the product of Example 3 (230 g) in ether (250 ml) is added dropwise. When the addition is complete the mixture is stirred an additional 16 hours. The reaction mixture is decomposed by careful addition of water (80 ml) followed by 15percent aqueous sodium hydroxide (80 ml) and additional water (240 ml). The resulting suspension is filtered, the filter cake washed with ethanol and ether and the combined filtrates evaporated to give a residue. Distillation of the residue gives the title product (155 g) (81percent) B.P. 75° C. (0.05 mm). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine; In dichloromethane;Cooling with ice; | To dichloromethane solution (100 ml) of 14 (6.38 g, 43.64 mmol), triethylamine (9.08 ml, 65.47 mmol) was added, and methane sulfonyl chloride (3.69 ml, 48.01 mmol) was dropped while cooling in ice with shaking, and stirred for 30 min at the same temperature. The reaction mixture was added cold water, and extracted with ethyl acetate. The extract was washed with water, dried, and evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (solvent: ethyl acetate/n-hexane = 1/2), to obtain 15 (9.66 g, 99percent) of oily light yellow substance. APCI-MS m/z 225[M+H]+ |
97.8% | With triethylamine; In dichloromethane;Cooling with ice; | (2,2-Dimethyl-1,3-dioxan-5-yl)methanol (1.0 g, 6.84 mmol) was dissolved in CH2C12 (30 mL) and cooled in ice bath. Triethylamine (1.14 mL, 8.21 mmol) was added, followed by methanesulfonyl chloride (0.586 mL, 7.52 mmol) and the reaction mixture was warmed to room temperature. The reaction mixture was washed with 0.1 N HCI, saturated aqueous NaHCO3, and the combined organic extracts were dried over sodium sulfate, filtered and concentrated to afford (2,2-dimethyl- 1 ,3-dioxan-5-yl)methyl methanesulfonate (1.5 g, 6.69 mmol, 97.8 percent yield) as a clear colorless oil. |
95% | With triethylamine; In dichloromethane; at 20℃; for 2h;Cooling; | Methanesulfonic acid 2 ,2-dimethyl- [ 1 ,3] dioxan-5-ylmethyl ester[0684] MsCl (4.4 mL, 56 mmol) was added slowly to a solution OfEt3N (9.8 mL, 71 mmol) and (2,2-dimethyl-[l,3]dioxan-5-yl)-methanol (6.87 g, 47.0 mmol) in CH2Cl2 (100 mL) at 0 0C (bath temp). The reaction mixture was stirred at rt for 2 h and then quenched with H2O (100 mL). The mixture was extracted with CH2Cl2 and <n="213"/>the organic fractions were dried (MgSO4) and concentrated in vacuo to give the title compound as a colorless liquid: yield 10.02 g (95percent).[0685] 1H NMR (400 MHz, CDCl3) delta (ppm): 4.42 (d, J= 7.4 Hz, 2H), 4.13-4.04 (m, 2H), 3.82-3.74 (m, 2H), 3.05 (s, 3H), 2.05-1.95 (m, IH), 1.46 (s, 3H), 1.40 (s, 3H). |
92% | With triethylamine; In dichloromethane; at -20℃; for 1h; | 10303] 2,2-Dimethyl-5-(hydroxymethyl)- 1 ,3-dioxane (3a) (5.00 g) was dissolved in 67 mE of CH2C12, and 5.42 mE of triethylamine was added thereto, followed by cooling to?20° C. Further, 2.56 mE of mesyl chloride (MsC1) was added, and the resulting mixture was stirred at ?20° C. for 1 hout Thereafter, 50 mE of water was added to the reaction mixture to stop the reaction, and extraction was performed twice with 40 mE of CH2C12. After the separated organic layers were washed with water, CH2C12 was distilled offunder reduced pressure, and the resulting residue was purifled with silica gel chromatography (n-hexane:ethylacetate=i :1) to obtain 6.22 g of compound (4a) (yield: 92percent).10304] ?H-NMR (500 MHz, CDC13):10305] oe: 1.39 (s, 3H), 1.46 (s, 3H), 2.00 (m, 1H), 3.04 (s,3H), 3.78 (dd, 2H, J=12, 3 Hz), 4.08 (dd, 2H, J=ii.5, 2.5 Hz), 4.42 (d, 2H, J=7 Hz) |
91% | With triethylamine; In dichloromethane; at 20℃; for 3h; | To a 500 mL round bottomed flask equipped with a magnetic stir bar containing DCM (200 mL) was placed 87 (5 g, 34 mmol, 1 equiv). To this solution was added mesyl chloride (4.3 <n="86"/>g, 38 mmol, 1.1 equiv), Et3N (5 g, 51 mmol, 1.5 equiv) and the reaction was allowed to stir at room temperature for 3 h. The reaction was then poured into water (100 mL) and extracted into DCM (3 x 100 mL). The combined organic extracts were washed with brine (100 mL), NaHCO3 solution (100 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified over silica gel. Product eluted out in 50percent EtOAc:Hexanes mixture in a gradient elution on a Combiflash purification system. Isolated 87 (7 g, 91percent) as a colorless solid. MS: [M+H]+: 225. |
84% | With triethylamine; In dichloromethane; at 0 - 20℃; for 16h; | [00652] Step B: Preparation of (2,2-dimethyl-1.3-dioxan-5-yl)methyl methanesulfonate: To a solution of (2,2-dimethyl-l,3-dioxan-5-yl)methanol (1.0 g, 6.84 mmol) in DCM (30 mL) at 0 °C was added triethylamine (1.43 mL, 10.3 mmol) followed by mesyl chloride (0.58 mL, 7.52 mmol). The mixture was allowed to warm slowly to ambient temperature over 16 hours then partitioned between 0.5 M HC1 (40 mL) and DCM (20 mL). The aqueous layer was extracted with DCM (2 x 20 mL) and the combined organic phases were washed with brine (20 mL), dried over Na2S04, filtered and concentrated (2,2-dimethyl-l ,3-dioxan-5-yl)methyl methanesulfonate (1.29 g, 84percent yield) as a colorless oil. ]H NMR (CDC13) delta 4.41 (d, J = 7.3 Hz, 2H), 4.08 (dd, J = 12.5, 3.6 Hz, 2H), 3.77 (dd, J = 12.5, 3.9 Hz, 2H), 3.04 (s, 3H), 2.03- 1.98 (m, 1H), 1.46 (s, 3H), 1.39 (s, 3H) ppm. |
With triethylamine; In dichloromethane; at 0 - 20℃; | Methanesulfonyl chloride(0.97 mL, 12.40 mmol) was added dropwise to a stirred solution of (2,2-dimethyl-1,3-dioxan-5-yl)methanol57 (18, 1.51 g, 10.33 mmol) and Et3N (2.18 mL, 15.49 mmol) in CH2Cl2 (10 mL) at 0 oC. The mixture was warmed to rt and stirred for 30 min then diluted with CH2Cl2 (20 mL) and washed with aq. NaHCO3 (sat., 3 x 10 mL) then dried and the solvent evaporated to give the crude mesylate as an oil. The latter was dissolved in DMF (7 mL),sodium thiomethoxide (1.45 g, 20.66 mmol) added and the mixture stirred at rt for 16 h. Diethyl ether (100 mL) was added and the solution washed with H2O (4 x 15 mL), brine (15 mL), dried and the solvent evaporated. The residue was chromatographed (EtOAc-hexanes,5:95) to give 19 as a colourless oil (1.38 g, 76percent). | |
With triethylamine; In dichloromethane; at -78 - 0℃; for 3h; | (2,2-Dimethyl-1,3- dioxan-5-yl)methanol (50 mg, 0.34 mmol) was dissolved in DCM (0.4mL). The mixture was cooled in to -78oC. Triethylamine (143 muL, 1mmol) and methanesulfonyl chloride (32 muL, 0.4 mmol) were added sequentially. The reaction mixture stirred at -78 ^C -> 0 ^C. After 3 hours, the reaction mixture was transferred to a separatory funnel, diluted with DCM, and washed with sodium bicarbonate. The organic layer was dried over sodium sulfate, filtered, and concentrated.1H NMR (600 MHz, Acetone-d6) ^ ppm 1.35 (d, J = 2.5 Hz, 3H) 1.42 (d, J = 2.9 Hz, 3H) 2.03 (td, J=7.2, 3.3 Hz, 1 H) 3.14 (d, J = 3.3 Hz, 3H) 3.74 - 3.83 (m, 2H) 4.04 - 4.15 (m, 2H) 4.39 (dd, J=7.2, 3.1 Hz, 2H); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triethylamine; In dichloromethane; at 0 - 20℃; for 1h; | 30.1.(2,2-dimethyl-1,3-dioxan-5-yl)methyl 4-methylbenzenesulfonateTo a solution of 1.5 g (10.26 mmol) of (2,2-dimethyl-1,3-dioxan-5-yl)methanol and 1.71 mL of Et3N in 15 mL of DCM, cooled to 0° C., are added 2.15 g (11.3 mmol) of tosyl chloride.The medium is allowed to warm to room temperature, and stirring is continued for 1 hour.The medium is taken up in 100 mL of DCM, washed successively with 0.1N HCl (2*20 mL) and brine (20 mL), dried over Na2SO4, concentrated under reduced pressure and then purified by chromatography on a column of silica gel, eluting with a 99/1 DCM/MeOH mixture.3 g of (2,2-dimethyl-1,3-dioxan-5-yl)methyl 4-methylbenzenesulfonate are obtained in the form of a colourless oil.Yield=97percent1H NMR, CDCl3, 400 MHz, delta (ppm): 7.8 (d, 2H); 7.3 (d, 2H); 4.1 (d, 2H); 3.9 (dd, 2H); 3.6 (dd, 2H); 2.4 (s, 3H); 1.9 (m, 1H); 1.4 (s, 3H); 1.2 (s, 3H) |
68.8% | With 1,4-diaza-bicyclo[2.2.2]octane; In dichloromethane; for 0.25h;Cooling with ice; | To a dried 50 mL round bottom flask were added compound Ii?-1 (470 mg, 3.22 mmol), DABCO (721.9 mg, 6.43 mmol) and CH2Cl2 (15 mL). With an ice bath, TsCl (675.3 mg, 3.54 mmol) was added slowly to the solution. After the solution was stirred for 15 minutes, TLC showed the disappearance of the raw materials. The mixture was diluted with CH2Cl2 (20 mL) when the reaction finished, and after filtration, the filtrate was washed in turn with hydrochloric acid (1 N, 15 mL), saturated aqueous sodium bicarbonate (15 mL) and saturated brine (15 mL). The organic phase was dried over anhydrous sodium sulfate, the solvent was evaporated under vacuum to give compound Ih?-1 (665 mg, 68.8percent). [0140] LC-MS (ESI): m/z=301 [M+H]+, 323 [M+Na]+. |
68.8% | With 1,4-diaza-bicyclo[2.2.2]octane; In dichloromethane; for 0.25h;Cooling with ice; | Example 8: Preparation of Compound Ih"-1: [0095] To a dried 50 mL round bottom flask were added compound Ii"-1 (470 mg, 3.22 mmol), DABCO (721.9 mg,6.43 mmol) and CH2Cl2 (15 mL). With an ice bath, TsCl (675.3mg, 3.54mmol) was added slowly to the solution. Afterthe solution was stirred for 15 minutes, TLC showed the disappearance of the raw materials. The mixture was dilutedwith CH2Cl2 (20 mL) when the reaction finished, and after filtration, the filtrate was washed in turn with hydrochloric acid(1 N, 15 mL), saturated aqueous sodium bicarbonate (15 mL) and saturated brine (15 mL). The organic phase wasdried over anhydrous sodium sulfate, the solvent was evaporated under vacuum to give compound Ih"-1 (665 mg, 68.8percent).LC-MS (ESI): m/z = 301 [M+H]+,323 [M+Na]+. |
With dmap; triethylamine; In dichloromethane; at 0 - 20℃; | A solution of (2,2-dimethyl-1 ,3-dioxan-5-yl)methanol (2.51 g, 17.1 mmol) and N, N- dimethylaminopyiridine (208 mg, 1.7 mmol) in dichloromethane (100 ml.) was cooled to 0 0C and p-toluenesulfonyl chloride (3.59 g, 18.8 mmol) and triethylamine (4.8 ml. 34.2 mmol) were added. The mixture was stirred overnight at rt, diluted with water, and the organic layer was separated. The solvent was removed and the crude material was purified via silica gel chromatography to give 4.16 g of the title compound. 1H NMR (DMSOd6) delta 7.78 (d, 2 H), 7.47 (d, 2 H), 4.09 (d, 2 H), 3.84 (dd, 2 H), 3.52 (dd, 2 H), 2.41 (s, 3 H), 1.79 - 1.94 (m, 1 H), 1.28 (s, 3 H), 1.18 (s, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With toluene-4-sulfonic acid; at 20℃; | (2, 2-Dimethyl-fl, 3] dioxan- 5 -yl) -methanol[0682] A solution of 2,2-dimethoxypropane (5.88 g, 56.5 mmol), 2-methyl- propane-l,3-diol (5.0 g, 47 mmol), and PTSA monohydrate (0.48 g, 2.3 mmol) in THF (100 mL) was stirred O/N at rt. The mixture was concentrated in vacuo to give the title compound as a colorless liquid: yield 6.87 g (99percent).[0683] 1H NMR (400 MHz, CDCl3) delta (ppm): 4.03 (dd, J= 11.7, 3.5 Hz, 2H), 3.84- 3.73 (m, 4H), 2.49-2.39 (m, IH), 1.90-1.80 (m, IH), 1.45 (s, 3H), 1.40 (s, 3H). |
95% | To tetrahydrofuran suspension (150 ml) of 13 (4.90 g, 46.17 mmol), acetone dimethyl acetal (6.56 ml, 53.54 mmol) and toluene sulfonic acid hydrate (0.26 g, 1.39 mmol) were added while shaking at room temperature, and stirred for 3 hours at room temperature. The reaction mixture was added triethylamine (3 ml), and evaporated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (solvent: chloroform/methanol = 10/1), to obtain 14 (6.38 g, 95percent) of oily colorless substance. APCI-MS m/z 147[M+H]+ | |
91% | With toluene-4-sulfonic acid; In tetrahydrofuran; at 20℃; for 2h; | To a 100 mL round bottomed flask equipped with a magnetic stir bar containing THF (75 mL) was placed a (4 g, 38 mmol, 1 equiv). To this solution was added b (4.5 g, 43 mmol, 1.15 equiv), PTSA (0.2 g, 1.1 mmol, 0.03 equiv) and the reaction was allowed to stir at room temperature for 2 h. After the reaction was complete, solvent was removed in vacuo. The residue was purified over silica gel. Product eluted out in 60percent EtOAc:Hexanes mixture in a gradient elution on a Combiflash purification system. Isolated 86 (5 g, 91percent) as a colorless oil. MS: [M+H]+: 147. |
73% | With toluene-4-sulfonic acid; at 20℃; for 51h; | Example 25 1 -(3 -(3 -hvdroxy-2-(hvdroxymethyl)propoxy)-4-methyl- 1 -phenyl- 1 H-pyrazol-5-yl)-3 -(2- phenyl-8-(trifluoromethyl)imidazo[ 1 ,2-a]pyridin-3-yl)urea [00651] Step A: Preparation of (2,2-dimethyl-l,3-dioxan-5-yl)methanol: To a suspension of 2-(hydroxymethyl)propane-l,3-diol (5.0 g, 47.1 mmol) in THF (100 mL) was added pTsOH (269 mg, 1.41 mmol) followed by 2,2-dimethoxypropane (6.72 mL, 54.7 mmol). The solution was stirred for 3 hours at ambient temperature then treated with pTsOH (200 mg) and stirred at ambient temperature for 48 hours. Triethylamine (3 mL) was added and the mixture concentrated under vacuum. The residue was purified silica column chromatography eluting with 5percent MeOH/DCM to afford (2,2-dimethyl-l,3-dioxan-5- yl)methanol (5.04 g, 73percent yield) as a colorless liquid. 1H NMR (CDC13) delta 4.02 (dd, J = 12.0, 4.1 Hz, 2H), 3.74-3.80 (m, 4H), 1.90 (t, J= 5.1 Hz, 1H), 1.78-1.88 (m, 1H), 1.45 (s, 3H), 1.40 (s, 3H) ppm. |
44% | With toluene-4-sulfonic acid; In tetrahydrofuran; at 20℃; for 60h; | 2-(Hydroxymethyl)-1 ,3-propanediol (1.0 g, 9.4 mmol), 2,2-bis(methyloxy)propane (2.3 ml_, 18.8 mmol) and p-toluenesulfonic acid monohydrate (0.09 g, 0.5 mmol) were <n="69"/>dissolved in THF and stirred for -60 h. To the solution was added triethyl amine (1.0 ml.) and the solvent was evaporated. Purification was accomplished by column chromatography (CH2CI2: MeOH) to afford the title compound (0.6 g, 44percent) as a oil. 1H NMR (400 MHz, DMSOd6): delta ppm 4.52 (t, 1 H), 3.80 (dd, 2 H), 3.59 (dd, 2 H), 3.36 (dd, 2 H), 1.63 - 1.72 (m, 1 H), 1.28 (d, 6 H). |
With toluene-4-sulfonic acid; In tetrahydrofuran; at 20℃; for 18h; | EXAMPLE 37 (2,2-Dimethyl-1 ,3-dioxan-5-yl)methanol; To a mixture of 2-(hydroxymethylpropane-1 ,3-diol (0.953 g) in THF (5 mL) was added 2,2- dimethoxypropane (1.28 mL) and p-toluenesulfonic acid monohydrate (0.053 g). The mixture was stirred at room temperature for 18 hours. Triethyl amine (0.028 g) was added and the mixture was concentrated under reduced pressure. The residue was chromatographed on silica gel (100 mL) using 10percent methanol in methylene chloride as eluent to give 0.963 g of the title compound: 1H NMR (CDCI3) delta 1.39 (s, 3 H), 1.44 (s, 3 H), 1.57 (m, 1 H), 1.83 (m, 1 H), 3.75 (m, 4 H), 4.01 (dd, 2 H). | |
With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; for 24h; | Example 3 Synthesis of (2,2-dimethyl-[l,3]dioxan-5-yl)-methanol3-1 3-2Triol 3-1 (1 eq.) was dissolved in DMF at a concentration of approximately 0.5 M and 2,2-dimethoxypropane (1.16 eq.) and p-toluenesulfonic acid monohydrate (0.03 eq.) were added. The solution was stirred for one or more days, and was quenched with TEA (0.5 eq.). As much solvent as possible was removed in vacuo and the remainder was purified by distillation under vacuum. | |
With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; for 24h; | Example 17; (2,2-dimethyl- [ 1 ,3] dioxan-5-yl)-methanol; 17-1 17-2Triol 17-1 (1 eq.) was dissolved in DMF at a concentration of approximately 0.5 M and 2,2-dimethoxypropane (1.16 eq.) and p-toluenesulfonic acid monohydrate (0.03 eq.) were added. The solution was stirred for one or more days, and was quenched with TEA (0.5 eq.). As much solvent as possible was removed in vacuo and 17-2 was purified by distillation under vacuum. | |
With toluene-4-sulfonic acid; In tetrahydrofuran; at 20℃; for 4h; | To a solution of 2-(hydroxymethyl)propane-l,3-diol (1 g) in THF (20 mL) were added 2,2-dimethoxypropane (1.344 mL) and para-toluenesulfonic acid monohydrate (0.054 g). The reaction mixture was stirred at room temperature for 4 hours, treated with TEA and concentrated. The concentrate was purified by flash chromatography (Analogix SF25chi40g with 20-30percent ethyl acetate/hexanes). MS (ESI) m/z 147.0 (M+l)+. | |
With toluene-4-sulfonic acid; In tetrahydrofuran; at 20℃; for 4h; | 24.1. (2,2-dimethyl-[1,3]dioxan-5-yl)-methanol To a mixture of 2-hydroxymethylpropane-1,3-diol (200 mg) in THF (1 ml) was added 2,2-dimethoxypropane (0.278 ml) and p-toluenesulfonic acid monohydrate (11 mg). The mixture was stirred at RT for 4 h. NEt3 (262 mul) was added and the mixture was stirred for further 15 min. The solvent was removed and the residue was purified by CC (DCM to DCM/MeOH 95/5) to afford 220 mg of the desired compound. 1H-NMR (CDCl3): 4.07 (d, 1H); 4.02 (d, 1H); 3.82 (d, 1H); 3.79 (m, 3H); 1.87 (m, 1H); 1.47 (s, 3H); 1.43 (s, 3H). | |
With toluene-4-sulfonic acid; In tetrahydrofuran; at 20℃; for 4h; | Example 24: 4-((S)-4-carboxy-2-[6-(3-hydroxy-2-hydroxymethyl-propoxy)-2-phenyl-pyrimidine-4-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester; 24.1. (2,2-dimethyl-[1,3]dioxan-5-yl)-methanol; To a mixture of 2-hydroxymethylpropane-1,3-diol (200 mg) in THF (1 ml) was added 2,2-dimethoxypropane (0.278 ml) and p-toluenesulfonic acid monohydrate (11 mg). The mixture was stirred at RT for 4 h. NEt3 (262 mul) was added and the mixture was stirred for further 15 min. The solvent was removed and the residue was purified by CC (DCM to DCM/MeOH 95/5) to afford 220 mg of the desired compound. 1H-NMR (CDCl3): 4.07 (d, 1H); 4.02 (d, 1H); 3.82 (d, 1H); 3.79 (m, 3H); 1.87 (m, 1H); 1.47 (s, 3H); 1.43 (s, 3H). | |
To a solution of 2-(hydroxymethyl)-1 ,3-propanediol (2.0 g, 18.8 mmol) in THF (40 ml.) were added 2,2-bis(methyloxy)propane (2.70 ml_, 21.7 mmol) and toluenesulfonic acid monohydrate (107 mg, 0.56 mmol). After stirring overnight at rt, additional 2,2- bis(methyloxy)propane (2.70 ml_, 21.7 mmol) was added and the reaction was stirred overnight. The reaction was neutralized with triethylamine (2 ml_), the solvent was removed and the crude material was purified via silica gel chromatography to give 2.51 g of the title compound. 1H NMR (DMSOd6) delta 4.49 (t, 1 H), 3.77 (dd, 2 H), 3.46 - 3.62 (m, 2 H), 3.33 (t, 2 H), 1.57 - 1.73 (m, 1 H), 1.25 (d, 6 H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Step 1: 5-(Benzyloxymethyl)-2,2-dimethyl-1,3-dioxane To a solution of (2, 2-dimethyl-1, 3-dioxan-5-yl)methanol (0.29 g, 2.0 mmol) in DMF (10 mL) was added NaH (60percent in oil, 0.12 g, 3.0 mmol) at 0° C. The mixture was stirred at 0° C. for 0.2 hours. Then (bromomethyl) benzene (0.45 g, 2.6 mmol) was added. The mixture was warmed to 10° C. for 3 h and held for 18 h. The reaction mixture was quenched with ice-water, followed by EtOAc (60 mL). Phase separation, the organic layer was washed with brine (60 mL*3), dried over Na2SO4 and filtered. The filtrate was concentrated and the residue was purified by silica gel column (20 g, UV 254 nm eluting with EtOAc in PE from 10percent to 50percent) to afford 5-(benzyloxymethyl)-2,2-dimethyl-1,3-dioxane (1), (0.46 g, 0.2 mol, 95percent) as a colorless oil. ESI-MS (EI+, m/z): 237.3 [M+H]+. | |
95% | To a solution of(2, 2-dimethyl-1, 3-dioxan-5-yl)methanol (0.29 g, 2.0 mmol) in DMF (10 mL) was added NaH (60percent in oil, 0.12 g, 3.0 mmol) at 0 °C . The mixture was stirred at 0 °C for 0.2 hours. Then (bromomethyl) benzene (0.45 g, 2.6 mmol) was added. The mixture was warmed to 10 °C for 3 h and held for 18 h. The reaction mixture was quenched with ice-water, followed by EtOAc (60 mL). Phase separation, the organic layer was washed with brine (60 mL*3), dried over Na2SO4 and filtered. The filtrate was concentrated and the residue was purified by silica gel column (20 g, UV 254 nm eluting with EtOAc in PE from 10 percent to 50 percent) to afford 5-(benzyloxymethyl)-2,2-dimethyl-1,3-dioxane (1), (0.46 g, 0.2 mol, 95 percent) as a colorless oil. ESI-MS (EI, m/z): 237.3 [M+H]. | |
To a solution of acetonide (2,2-dimethyl-1,3-dioxan-5-yl)methanol (3.0 g, 20.52 mmol) and tetrabutyl ammonium iodide (7.58 g, 20.52 mmol) in anhydrous THF (100 mL) was added sodium hydride (1.108 g, 27.7 mmol) in 3 portions. The mixture was allowed to stir at room temperature for 1 hour and then treated with benzyl bromide (2.93 ml, 24.63 mmol) over 3 minutes. The mixture was allowed to stir overnight at room temperature (18 hours). The mixture was analyzed by tlc (2:1 hexanes:ethyl acetate) and 1H NMR which showed complete consumption of starting material. The mixture was quenched with saturated ammonium chloride solution (75 mL) and extracted with ethyl acetate (200 mL and 100 mL). Combined organic phases were dried over sodium sulfate and then concentrated to dryness. The crude material was then purified by column chromatography over silica gel eluting with 0-30percent EtOAc/hexanes to obtain MD-02-130 as colorless oil. 1H NMR (400 MHz, chloroform-d) delta 7.35 - 7.24 (m, 5H), 4.50 (s, 2H), 3.96 (dd, J = 12.0, 4.2 Hz, 1H), 3.77 (dd, J = 11.8, 6.4 Hz, 1H), 3.51 (d, J = 6.7 Hz, 2H), 2.04 - 1.97 (m, 1H), 1.41 (s, 3H), 1.38 (s, 3H). |
To a solution of compound 24 (crude material max. 94 mmol)in dry DMF (600 ml) cooled to 0 C under argon atmosphere and NaH (60percent suspension in mineral oil; 6 g, 150 mmol, 1.6 eq.) was added. Reaction flask was filled with argon again and the mixture was stirred for 20 min. to preform sodium salt of alcohol. Benzylbromide (14.6 ml, 123 mmol, 1.3 eq.) was added and reaction flask was filled with argon again. The resulting mixture was let to warmto room temperature and stirred overnight. Water (100 ml) was added and mixture was stirred for 30 min. Solvent was evaporated in vacuo and the residue was codistilled with toluene (3). Crude material was suspended in EtOAc (250 ml) and mixture of saturatedsolution of NH4Cl (20 ml) and water (180 ml) was added.Water phase was extracted with EtOAc (2 150 ml). The organic phase was collected (250 + 150 + 150 ml) and washed with water(2 200 ml), followed by brine (1 200 ml) and dried overMgSO4. The solution was filtered and evaporated in vacuo. The residue(crude compound 25, red-brown oil) was diluted in MeOH(700 ml) and water (70 ml). DOWEX (50WX8 H+, 30 g) was addedand the mixture was heated at 50 C and stirred overnight. Reactionmixture was cooled down to room temperature and filteredthrough the frit (S3), evaporated in vacuo and codistilled withtoluene (3). Crude product 26 was obtained as brown oil andused in the next reaction step without purification. Reaction wasmonitored by TLC. Small amount of crude product was purifiedby flash chromatography (silica gel; eluent CHCl3/MeOH, gradient2?15percent) to obtain an analytical sample |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.8% | A mixture of 2-(hydroxymethyl)-1,3-propanediol (4.09 g, 38.5 mmol), acetone (130 ml, 1768 mmol) and 70percent perchloric acid (1.37 g, 9.55 mmol) was stirred at room temperature for 21 hours. After the pH of the reaction mixture was adjusted with concentrated aqueous ammonia to 9, the reaction mixture was concentrated. The residue was purified by silica gel column chromatography (silica gel: 100 g, elution solvent: heptane, heptane/ethyl acetate=1/3) to obtain the title compound (4.83 g, yield: 85.8percent) as a colorless oil. 1H NMR(400 MHz, DMSO-d6) deltappm; 1.29(3H, s), 1.30(3H, s), 1.64-1.74(1H, m), 3.35-3.41(2H, m), 3.61(2H, dd, J=7, 12 Hz), 3.82(2H, dd, J=4, 12 Hz), 4.54(1H, t, J=5 Hz). | |
85.8% | With perchloric acid; In water; at 20℃; for 21h; | A mixture of 2-(hydroxymethyl)-1,3-propanediol (4.09 g, 38.5 mmol), acetone (130 ml, 1.768 mmol) and 70percent perchloric acid (1.37 g, 9.55 mmol) was stirred for 21 hours at room temperature. The reaction mixture was concentrated after adjusting to pH 9 with concentrated ammonia. The residue was purified by silica gel column chromatography (silica gel: 100 g, elution solvent: heptane, heptane/ethyl acetate = 1/3) to obtain the target compound (4.83 g, yield: 85.8percent) as a colorless oily substance. 1H-NMR (400 MHz, DMSO-d6) deltappm: 1.29 (3H,s), 1.30 (3H,s), 1.64-1.74 (1H,m), 3.35-3.41 (2H,m), 3.61 (2H,dd,J=7,12 Hz), 3.82 (2H,dd,J=4,12 Hz), 4.54 (1H,t,J=5 Hz) |
85.8% | With perchloric acid; In water; at 20℃; for 21h; | (Production Example 1) (2,2-dimethyl-1,3-dioxan-5-yl)methanol [Show Image] A mixture of 2-(hydroxymethyl)-1,3-propanediol (4.09 g, 38.5 mmol), acetone (130 ml, 1768 mmol) and 70percent perchloric acid (1.37 g, 9.55 mmol) was stirred for 21 hours at room temperature. The pH of the reaction mixture was adjusted to 9 with concentrated aqueous ammonia and the reaction mixture was concentrated. The residue was purified by silica gel column chromatography (silica gel: 100 g, elution solvent: heptane, heptane/ethyl acetate= 1/3) to produce the title compound (4.83 g, yield: 85.8percent) as a colorless oil. 1H NMR (400 MHz, DMSO-d6) delta ppm; 1.29 (3H, s), 1.30 (3H, s), 1.64-1.74 (1H, m), 3.35-3.41 (2H, m), 3.61 (2H, dd, J=7, 12Hz), 3.82 (2H, dd, J=4, 12Hz), 4.54 (1H, t, J=5Hz). |
85.8% | perchloric acid; In water; at 20℃; for 21h; | (1 ) (2.2-Dimethyl-1.3-dioxan-5-vpimethanolA mixture of 2-(hydroxymethyl)-1 ,3-propanedior(4.09 g, 38.5 mmol), acetone (130 ml, 1768 mmol), and 70percent perchloric acid (1.37 g, 9.55 mmol) was stirred at room temperature for 21 hours. A pH of the reaction mixture was adjusted to 9 using concentrated ammonia water, and then subjected to concentration. The residue was purified by silica gel column chromatography (silica gel: 100 g, eluent: heptane, heptane / ethyl acetate = 1 / 3), whereby the title compound (4.83 g, percentage yield 85.8percent) was obtained as a colorless oil. 1H-NMR (400 MHz, DMSO-d6) delta ppm: 1.29 (3H, s), 1.30 (3H, s), 1.64-1.74 (1 H, m), 3.35-3.41 (2H1 m), 3.61 (2H, dd, J = 7, 12 Hz), 3.82 (2H, dd, J = 4, 12 Hz), 4.54 (1 H, t, J = 5 Hz). |
To a solution of 2-hydroxymethyl-1,3-propanediol (20 g,189 mmol) in dry acetone (600 ml) freshly annealed molecularsieves (4A) and p-toluenesulfonic acid monohydrate (2 g,10.5 mmol) were added. Reaction mixture was stirred overnightat room temperature. Mixture was filtered over kieselguhr. Tothe filtrate DOWEX (D1 OH-, 7 g) was added and the mixture washeated to 40 C and stirred for 30 min. Suspension was filtered overfrit (S3) and Et3N (0.5 ml) was added to the filtrate for stabilization.Solvent was evaporated in vacuo and obtained crude material wasdried under vacuum. Crude product 24 was obtained as colourlessoil and used in the next reaction step without purification. Reactionwas monitored by TLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With tetrachloromethane; triphenylphosphine; for 8h;Reflux; | The solution of S3 (73 g, 0.5 mol)and PPh3 (170 g, 0.65 mol) in dry CCl4 (300 mL) was refluxed for 8 hours. The mixture was filtered and the precipitate was washed by CCl4 (100 mL) and hexane(300 mL). The solvents were evaporated, the residue was dissolved in diethyl ether(200 mL) and filtered again. The ether was evaporated and the residual oil was distilled yielding S3 (54 g, 65percent) as colorless liquid 4. 1H NMR (700 MHz, CDCl3, 300K): delta = 4.04 (dd, J = 3.9 Hz, 12.2 Hz, 2H), 3.81 (dd, J = 5.1 Hz,12.0 Hz, 2H), 3.67 (d, J = 7.1 Hz, 2), 1.99-1.92 (m, 1H), 1.45 (s, 3H), 1.41 (s, 3H). |
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