| 99% |
With DL-10-camphorsulphonic acid In acetonitrile at 20℃; for 4h; |
|
| 95% |
With copper(II) bis(trifluoromethanesulfonate) In acetonitrile for 1.5h; Inert atmosphere; Sonication; |
|
| 95% |
With DL-10-camphorsulphonic acid In acetonitrile for 5h; Reflux; |
In the first approach, the present invention employs highly purified methyl-a-D- glucopyranoside (Aldrich, min. 99% purity) as a starting material for the synthesis of Monomer A. This process eliminates the possibility of the presence of any β-anomer in the final product. Thus, methyl-a-D-glucopyranoside is converted to the desired building block according to the scheme depicted below. During the further synthetic manipulations toward preparing Fondaparinux from Building Block A there are no synthetic operations that can epimerize the anomeric center in this monomer. This strategy affords a-methyl-2-azido-3-benzyl-6-benzoyl-D- glucoside free from its β-anomer. |
| 94% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 60℃; |
|
| 93% |
With DL-10-camphorsulphonic acid In N,N-dimethyl-formamide at 70℃; for 5h; Inert atmosphere; |
1 Synthesis of 4,6-O-benzylidene-α-D-methylglucopyranoside (2
α-D-methyl glucopyranoside 1 (19.41 g, 100 mmol), PhCH (OMe) 2 (30.44 g, 200 mmol) and CSA (2.00 g) were dissolved in dry DMF (150 mL) and heated at 70 ° C. for 5 h under N2 atmosphere, At this point TLC test found that the reaction was completed. The reaction mixture was cooled and poured into ice-water (500 mL) Stirred and extracted rapidly with CH 2 Cl 2 (200 mL × 3). The combined extracts, Washed sequentially with 2% NaHCO3 solution (100 mL) and 10% brine (200 mL) Dried over anhydrous Na2SO4, the solvent was evaporated on a rotary evaporator, The resulting residue was purified by column chromatography to give 26.25 g of 2 as a white solid in 93% yield, m.p. 163.5-165.5 deg C. |
| 92% |
With DL-10-camphorsulphonic acid In chloroform at 65℃; |
|
| 92% |
With stannous chloride In acetonitrile at 80℃; for 1h; |
|
| 91% |
With 3,4-bis((3,5-bis(trifluoromethyl)phenyl)amino)cyclobut-3-ene-1,2-dione In acetonitrile at 20℃; for 1h; Inert atmosphere; |
|
| 91% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 60℃; for 4h; |
|
| 90% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 70℃; for 4h; |
|
| 90% |
With toluene-4-sulfonic acid In acetonitrile at 20℃; for 12h; |
|
| 90% |
With iodine In acetonitrile at 20℃; for 1h; |
|
| 90% |
With silica-supported perchloric acid In PEG 600 at 20℃; for 6h; |
|
| 90% |
With copper(II) bis(trifluoromethanesulfonate) In acetonitrile at 20℃; for 3h; Sonication; Schlenk technique; Inert atmosphere; |
|
| 87% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 45℃; |
|
| 86% |
With ferric(III) chloride In acetonitrile at 20℃; for 3.5h; regioselective reaction; |
|
| 86% |
With DL-10-camphorsulphonic acid In acetonitrile at 20℃; for 48h; |
|
| 85% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 20℃; for 6h; |
|
| 85% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 60℃; for 3h; |
|
| 84% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide; acetonitrile |
|
| 83% |
With DL-10-camphorsulphonic acid In chloroform for 6h; Heating; |
|
| 83% |
With DL-10-camphorsulphonic acid In N,N-dimethyl-formamide at 60℃; |
|
| 83% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 20℃; for 0.116667h; sonication; |
|
| 83% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 40℃; |
|
| 82% |
With pyridinium 4-toluenesulfonate In N,N-dimethyl-formamide at 85℃; for 2h; |
|
| 81.5% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 40 - 80℃; for 5h; |
|
| 81% |
With DL-10-camphorsulphonic acid In acetonitrile for 0.75h; Reflux; Inert atmosphere; |
|
| 81% |
With DL-10-camphorsulphonic acid In acetonitrile at 50℃; |
|
| 80% |
With DL-10-camphorsulphonic acid In acetonitrile at 80℃; for 0.333333h; |
|
| 80% |
With DL-10-camphorsulphonic acid In acetonitrile at 80℃; for 0.333333h; |
|
| 80% |
With toluene-4-sulfonic acid |
|
| 78% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide for 1h; |
|
| 76% |
With CSA In acetonitrile at 85℃; for 6h; |
|
| 75% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 55℃; Inert atmosphere; |
|
| 75% |
With iodine In N,N-dimethyl-formamide at 20℃; for 12h; |
|
| 74% |
With DL-10-camphorsulphonic acid In acetonitrile at 20℃; for 0.75h; Inert atmosphere; Reflux; |
|
| 73% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 50℃; for 2h; |
|
| 73% |
With toluene-4-sulfonic acid In water monomer; N,N-dimethyl-formamide at 84℃; for 1.5h; Inert atmosphere; |
|
| 73% |
With DL-10-camphorsulphonic acid In acetonitrile for 0.333333h; Reflux; Dean-Stark; |
|
| 73.6% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide |
Preparation of methyl 4,6-O-benzylidene-α-D-glucopyranoside (Glc-1)
Following the reported method. [1] To a solution of methyl α-D-glucopyranoside (Glc,6.0 g, 30.9 mmol) in anhydrous DMF (25 mL) was added PhCH(OMe)2 (7.0 ml,46.3 mmol) and the solution was acidified with p-TsOHH2O (0.7 g, 3.1 mmol) topH 3. The reaction was stirred at 50°C for 4 h and was neutralized with 3 mL of TEA.Then, the reaction mixture was poured into saturated solution of NaHCO3 and extracted with 300 mL of EtOAc. The resulting extract was washed with H2O. Theorganic extracts were dried over anhydrous Na2SO4 and then concentrated underreduced pressure. The residue was lyophilized to dryness overnight to afford Glc-1as a white solid (6.3 g, 73.6%; Rf = 0.6, CHCl3: MeOH = 9: 1). 1H NMR data (400MHz, CD3OD): δ 7.51 - 7.49 (2H, H-2Ar and H-6Ar, overlap), 7.37 - 7.33 (3H, H-3Ar,H-4Ar, H-5Ar, overlap), 5.56 (1H, s, PhCHO2), 4.73 (1H, d, J = 3.8 Hz, H-1), 4.20(1H, dd, J = 15.3, 5.5 Hz, H-6a), 3.82 (1H, t, J = 9.4 Hz, H-3), 3.78 - 3.70 (2H, H-5and H-6b, overlap), 3.52 (1H, dd, J = 9.3, 3.8 Hz, H-2), 3.43 (1H, m, H-4), 3.42 (3H,s, OCH3). 13C NMR data (101 MHz, CD3OD): δ 139.2 (Ar-C), 129.9, 129.0(2),127.5(2) (Ar-CH), 103.0 (PhCHO2), 102.0 (C-1), 82.9 (C-4), 74.1 (C-2), 72.0 (C-3),70.0 (C-5), 63.9 (C-6), 55.8 (OCH3). ESI-MS: (m/z) [M+Na]+ 305.5. |
| 73% |
With camphor sulfuric acid In acetonitrile Reflux; Inert atmosphere; |
|
| 72% |
With dodeca-tungstophosphoric acid In acetonitrile at 0℃; Molecular sieve; Inert atmosphere; |
|
| 70% |
With DL-10-camphorsulphonic acid In chloroform at 350℃; for 9h; Dean-Stark; Molecular sieve; Reflux; |
|
| 65% |
With DL-10-camphorsulphonic acid In acetonitrile for 0.333333h; Reflux; |
8
0236| Mi hyl-4,6- -beBaEySi(Jee--I -gcopyraiiosiile (41). To a solution containing 1 .0 g (51 ,5 mmoi) of a-D-raethyl glueopyranoside in 200 mL of acetonitriie was added 14.0 mL (14.2 g, 92.7 tnmo) of benxaldehyde dimethyl acetai and 600 rag (2,57 mmoi) of camphor si Ionic acid. The reaction mixture was heated to reflux for 20 mm and then allowed to cool to room temperature and neutralized by the addition of 400 uJL of triethySamine. The reaction mixture vvas diluted with 800 mL of ethyl acetate. The organic layer was washed with three 250-mL portions of water and dried (MgSQ ). The organic laye was concentrated under diminished pressure to afford a crude residue. The residue was crystallized from 1 :7 dichloroniethane-hexanes to afford acetai 41 as a colorless solid: yield. 9.48 g (65%); silica gel TLC Rf 0.1 (2: i ethyl acetate-hexanes); fH NMR (CDC ) 5 3.45-3.47 (m, 4H), 3.63 (dd, IH, J" 9.1 and 3.9 Hz), 3.71-3.85 (m5 2H), 3.93 (t, 1H, J '= 9.2 .z), 4.29 (dd, 1H, J= 9.7 and 4.3 Hz), 4.80 (d, JH, = 3.9 Hz), 3.53 (s, I H) aad 7.33-7.53 (m, 5H); : NMR (CDCfe) δ 55.7, 62.5, 69. L 72.0, 73.0, 81.0, 99.9, 102.1 , 126.4, 137.2. |
| 63% |
With pyridinium 4-toluenesulfonate In N,N-dimethyl-formamide at 80℃; |
|
| 60% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 60℃; |
|
| 53% |
With DL-10-camphorsulphonic acid In acetonitrile at 20℃; for 2h; |
|
| 42% |
Stage #1: methyl-α-D-glucopyranoside With DL-10-camphorsulphonic acid for 1h;
Stage #2: benzaldehyde dimethyl acetal In acetonitrile at 20℃; for 11h; |
|
| 34% |
With toluene-4-sulfonic acid In N,N-dimethyl-formamide for 0.116667h; Sonication; |
1.1.6
(1.6) 5 ml of DMF was added to (+)-α-methyl-D-glucose (7) (500 mg, 2.58 mmol), benzaldehyde dimethylacetal (412 mg, 2.71 mmol) and p-toluenesulfonic acid monohydrate (491 mg, 2.58 mmol), and the mixture was subjected to a sonication treatment for 7 minutes. Triethylamine was added to the reaction mixture, and the mixture was filtered and concentrated under a reduced pressure to give a crude product. The crude product was purified by separating by silica gel column chromatography (elution solvent: chloroform/methanol = 20/1) to give (+)-(4,6-O-benzylidene)methyl-α-D-glucopyranoside (8) (yield amount: 248 mg, yield: 34%), as shown in the following chemical reaction formula. The result of the physical and chemical analysis of this by 1H NMR is shown below. 1H NMR (CDCl3) δ = 7.48 (dd, J = 3.6 Hz, J = 3.0 Hz, 2H), 7.35-7.39 (m, 3H), 5.49 (s, 1H), 4.71 (d, J = 4.0 Hz, 1H), 4.26 (dd, J = 5.6 Hz, J = 4.2 Hz, 1H), 3.89 (t, J = 9.6 Hz, 1H), 3.69-3.80 (m, 2H), 3.56 (dd, J = 5.2Hz, J = 3.8 Hz, 1H), 3.44 (t, J = 9.4 Hz, 1H), 3.40 (s, 3H) |
| 29% |
With DL-10-camphorsulphonic acid In acetonitrile Reflux; |
5
As shown in Scheme 5, the benzylidene was formed on compound 38 with benzaldehyde diemthyl acetal (49) and catalytic camphorsulfonic acid (CSA). Diol 50 was protected as benzyl ethers to give compound 51a 84% yield. |
|
With DL-10-camphorsulphonic acid In N,N-dimethyl-formamide at 100℃; for 2h; |
|
|
With toluene-4-sulfonic acid |
|
|
With DL-10-camphorsulphonic acid In chloroform Heating; |
|
|
With perchloric acid on silica gel In acetonitrile at 20℃; for 0.5h; |
|
|
With toluene-4-sulfonic acid In N,N-dimethyl-formamide |
|
|
With toluene-4-sulfonic acid In acetonitrile at 20℃; for 5h; |
|
|
With toluene-4-sulfonic acid |
|
|
With toluene-4-sulfonic acid In aceonitrile for 17h; Inert atmosphere; Reflux; |
|
|
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 40℃; |
|
|
With 10-camphorsufonic acid In chloroform at 68℃; for 2h; |
|
|
With iodine In acetonitrile at 20℃; for 3h; |
|
|
With DL-10-camphorsulphonic acid In acetonitrile at 35℃; for 4h; Inert atmosphere; |
|
|
With DL-10-camphorsulphonic acid In acetonitrile at 20℃; for 48h; |
|
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
