Sodium Bicarbonate → HCID 67432952, compound
Reaction equation
[C:1]([O:9][CH2:10][C@@H:11]1[C@@H:15]([O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:14]([F:25])[C@H:13]([N:26]2[CH:34]=[N:33][C:32]3[C:27]2=[N:28][CH:29]=[N:30][C:31]=3[NH2:35])[C:12]1(O)[CH2:36]O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+]>C(#N)C>[C:1]([O:9][CH2:10][C@@H:11]1[C@@H:15]([O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:14]([F:25])[C@H:13]([N:26]2[CH:34]=[N:33][C:32]3[C:27]2=[N:28][CH:29]=[N:30][C:31]=3[NH2:35])[C:12]1=[CH2:36])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -30 °C
Procedure
Compound 13 (260 mg, 0.50 mmol) was dissolved in moist acetonitrile (9 μL H2O was added into 10 mL anhydrous acetonitrile) and cooled to −30° C. Excess 1-bromocarbonyl-methylethylacetate (0.54 mL, 3.68 mmol) was added dropwise into the mixture and allowed to warm up to room temperature. After stirring at room temperature for 1 h, the reaction mixture was again cooled to −30° C. and additional 1-bromocarbonyl-methylethylacetate (0.2 mL, 1.47 mmol) was added. Crushed ice was added to quenched the reaction and neutralized with saturated NaHCO3 (20 mL) solution and extracted with EtOAc (100 mL×2). The combined organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was dissolved in anhydrous DMF and treated with activated zinc (c.a. 2.0 g) and HOAc (0.2 mL) and stirred at room temperature for 8 h. The volatile was removed in vacuo and the residue was dissolved in isopropyl alcohol/chloroform (4:1) co-solvent and washed with saturated NaHCO3 (15 mL) solution, H2O and brine. The organic layer was colleted and dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on a silica gel (EtOAc:Hexanes=2:1 to 4:1) to give exo-cyclic alkene nucleoside 14 (165.0 mg, 68%) as a white solid. mp: 195-198° C. (dec.) [α]25D +77.66° (c 0.27, CHCl3); UV (MeOH) λmax 231.0, 259.0 nm; 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 8.12-8.06 (m, 2H), 7.94 (d, J=3.6 Hz, 1H), 7.65-7.44 (m, 3H), 6.0 (dd, J=2.4 and 33.2 Hz, 1H), 5.86 (br, 2H, D2O exchangeable), 5.75 (d, (d, J=14.8 Hz, 1H), 5.50 (s, 1H), 5.21 (dd, J=4.0 and 50.8 Hz, 1H), 4.98 (d, J=1.2 Hz, 1H), 4.82-4.64 (m, 1H), 4.66-4.61 (m, 1H), 3.42 (m, 1H); 13C NMR (100 MHz, CDCl1) δ 166.4, 165.0, 155.5, 153.2, 150.5, 144.4, 140.9, 140.8, 133.8, 133.3, 130.0, 129.7, 129.6, 128.7, 128.6, 128.5, 118.8, 113.2, 93.6 (d, J=184.4 Hz), 75.8 (d, J=29.0 Hz), 64.4 (d, J=3.1 Hz), 58.3 (d, J=17.5 Hz), 46.5. FIR-MS Calcd. for (C26H22FN5O4+H)+488.1734, found 488.1731.
Workup
- temperatureto warm up to room temperature
- temperaturethe reaction mixture was again cooled to −30° C.
- additionCrushed ice was added
- customto quenched
- customthe reaction
- extractionextracted with EtOAc (100 mL×2)
- washThe combined organic layer was washed with brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationThe filtrate was concentrated in vacuo
- dissolutionthe residue was dissolved in anhydrous DMF
- additiontreated with activated zinc (c.a. 2.0 g) and HOAc (0.2 mL)
- stirringstirred at room temperature for 8 h
- customThe volatile was removed in vacuo
- dissolutionthe residue was dissolved in isopropyl alcohol/chloroform (4:1) co-solvent
- washwashed with saturated NaHCO3 (15 mL) solution, H2O and brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationThe filtrate was concentrated in vacuo
- customthe residue was purified by column chromatography on a silica gel (EtOAc:Hexanes=2:1 to 4:1)
Sources & evidence
- ORD record
- ord-74ef92683b8f46d1bf4849e68a22854e
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08946244B2
Reaction notes
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