Thymine → HCID 15334393, compound

HRID 659833Notes

Reaction equation

HRID 659833 reaction equation
[CH2:1]([C@@:4]1([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:12]([CH2:13][O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:11][CH:6](OC(=O)C)[C@@H:5]1[O:22][C:23](=[O:25])[CH3:24])[CH:2]=[CH2:3].[NH:34]1[CH:42]=[C:40]([CH3:41])[C:38](=[O:39])[NH:37][C:35]1=[O:36].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(=O)([O-])O.[Na+]>C(#N)C>[C:23]([O:22][C@@H:5]1[C@:4]([CH2:1][CH:2]=[CH2:3])([O:26][CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C@@H:12]([CH2:13][O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:11][C@H:6]1[N:34]1[CH:42]=[C:40]([CH3:41])[C:38](=[O:39])[NH:37][C:35]1=[O:36])(=[O:25])[CH3:24]

Participants

7

Reactant 5

HCID 1135ThymineHCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 54105883HCID 54105883, compound

Product 1

HCID 15334393HCID 15334393, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of the anomeric mixture 0C (β:α˜2:1, 11.8 g, 26.0 mmol) (P. Nielsen, H. M. Pfundheller and J. Wengel, Chem. Commun., 1997, 825; P. Nielsen, H. M. Pfundheller, C. E. Olsen and J. Wengel, J. Chem. Soc., Perkin Trans. 1, 1997, in the press) and thymine (6.55 g, 52.0 mmol) in anhydrous acetonitrile (250 cm3) was added N,O-bis(trimethylsilyl)acetamide (44.9 cm3, 182 mmol). The reaction mixture was stirred at reflux for 1 h and cooled to 0° C. Trimethylsilyl triflate (8.00 cm3, 44.0 mmol) was added dropwise and the solution was stirred at room temperature for 12 h. An ice-cold saturated aqueous solution of sodium hydrogencarbonate (270 cm3) was added and the mixture was extracted with dichloromethane (3×125 cm3). The organic phase was washed with saturated aqueous solutions of sodium hydrogencarbonate (2×125 cm3) and brine (2×125 cm3) and dried (Na2SO4). The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography using dichloromethane/methanol (98:2, v/v) as eluent to give nucleoside 1 as a white solid material (11.6 g, 86%). δH (CDCl3) 8.64 (1H, br s, NH), 7.75 (1H, d, J 1.1, 6-H), 7.41-7.25 (10H, m, Bn), 6.43 (1H, d, J 8.2, 1′-H), 5.88 (1H, m, 2″-H), 5.66 (1H, d, J 8.2, 2′-H), 5.12 (1H, s, 3″-Ha), 5.07 (1H, dd, J 1.5, 8.5, 3″-Hb), 4.85 (1H, d, J 11.2, Bn), 4.64 (2H, s, Bn), 4.63 (1H, d, J 11.2, Bn), 4.33 (1H, br s, 4′-H), 3.81 (1H, dd, J 2.7, 11.1, 5′-Ha), 3.65 (1H, m, 5′-Hb), 2.81-2.65 (2H, m, 1″-Ha, 1″-Hb), 2.08 (3H, s, COCH3), 1.52 (3H, d, J 0.8, CH3). δC (CDCl3) 170.1 (C═O), 163.6 (C-4), 150.9 (C-2), 138.1, 136.6 (Bn), 136.0 (C-6), 131.6 (C-2″), 128.8, 128.4, 128.3, 127.6, 127.5, 127.1 (Bn), 118.5 (C-3″), 111.1 (C-5), 84.2, 83.4, 83.1, 77.4 (C-1′, C-2′, C-3′, C-4′), 73.6, 69.2 (Bn), 65.6 (C-5′), 33.7 (C-1″), 20.8 (COCH3), 11.9 (CH3) (Found. C, 66.8; H, 6.3; N, 5.1. C29H32N2O7 requires C, 66.9; H, 6.2; N, 5.4%).

Workup

  1. temperatureat reflux for 1 h
  2. stirringthe solution was stirred at room temperature for 12 h
  3. extractionthe mixture was extracted with dichloromethane (3×125 cm3)
  4. washThe organic phase was washed with saturated aqueous solutions of sodium hydrogencarbonate (2×125 cm3) and brine (2×125 cm3)
  5. dry with materialdried (Na2SO4)
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-dcc7c970de02426084b84da8ded80cdc
Source dataset
uspto-grants-2011_12
Patent number
US08080644B2

Reaction notes

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