Tetrabutylammonium Fluoride → 3'-[(Acetyloxy)methyl]-3'-deoxythymidine

HRID 2288279Notes

Reaction equation

HRID 2288279 reaction equation
[Si]([O:18][CH2:19][C@H:20]1[O:24][C@@H:23]([N:25]2[CH:33]=[C:31]([CH3:32])[C:29](=[O:30])[NH:28][C:26]2=[O:27])[CH2:22][C@@H:21]1[CH2:34][O:35][C:36](=[O:38])[CH3:37])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.CCOC(C)=O>[C:36]([O:35][CH2:34][C@@H:21]1[C@@H:20]([CH2:19][OH:18])[O:24][C@@H:23]([N:25]2[CH:33]=[C:31]([CH3:32])[C:29](=[O:30])[NH:28][C:26]2=[O:27])[CH2:22]1)(=[O:38])[CH3:37]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 21969455HCID 21969455, compound

Product 1

HCID 219694523'-[(Acetyloxy)methyl]-3'-deoxythymidineYield 57%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Compound 183 (2.00 g, 3.73 mmol) was dissolved in dry THF (36 ml) and tetrabutylammonium fluoride (8.8 ml, 1.0 M solution in THF, 2.4 equiv.) was added via syringe at room temperature under an atmosphere of argon. After completion of the reaction (1.5 hours), as was monitored by tlc in EtOAc (Rf 0.42), the solvent was removed in vacuo. The residue was purified by silica gel flash column chromatography in EtOAc/Hexane (4:6-9:1, v/v) to afford 184 (0.63 g, 57%) 1H NMR (CDCl3): δ8.89 (br, 1 H, NH), 7.55 (d, 1 H, J=1.1 Hz, H6), 6.13 (dd, 1 H, J=4.9, 6.6 Hz, H-1'), 4.17 & 4.09 (m, 2 H, CH2 -OAc), 4.07 (d, 1 H, J=11.7 Hz, H-5' & H-5'), 3.94-3.90 (m, 1 H, H-4'), 3.76 (d, 1H, J=11.7 Hz, H-5), 2.80-2.76 (m, 1 H, H-3'), 2.60 (br, 1 H, OH), 2.29-2.25 (m, 2 H, H2' & H-2"), 2.09 (s, 3 H, COCH3), 1.91 (s, 9 H, C(CH3)3); 13C NMR (CDCl3): 170.8 (C=O), 163.8 (C4), 150.3 (C2), 136.3 (C6), 110.8 (C5), 85.4 (C1'), 83.5 (C4'), 64.2 (C5'), 36.8 (C3'), 35 35.6 (C2'), 20.8, 12.5;

Workup

  1. customAfter completion of the reaction (1.5 hours)
  2. customthe solvent was removed in vacuo
  3. customThe residue was purified by silica gel flash column chromatography in EtOAc/Hexane (4:6-9:1

Sources & evidence

ORD record
ord-5fa0a808d94748b3bf096bcd1495aa89
Source dataset
uspto-grants-2000_07
Patent number
US06087482

Reaction notes

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