N-bromobutanimide → 5'-O-tert-butyldimethylsilyloxy-5-bromomethyl-2',3'-dideoxyuridine

HRID 76962Notes

Reaction equation

HRID 76962 reaction equation
[Si:1]([O:8][O:9][CH2:10][C@H:11]1[O:15][C@@H:14]([N:16]2[CH:24]=[C:22]([CH3:23])[C:20](=[O:21])[NH:19][C:17]2=[O:18])[CH2:13][CH2:12]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1C(=O)N([Br:32])C(=O)C1>C(Cl)(Cl)(Cl)Cl>[Si:1]([O:8][O:9][CH2:10][C@H:11]1[O:15][C@@H:14]([N:16]2[CH:24]=[C:22]([CH2:23][Br:32])[C:20](=[O:21])[NH:19][C:17]2=[O:18])[CH2:13][CH2:12]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 87364841HCID 87364841, compound

Product 1

HCID 873646485'-O-tert-butyldimethylsilyloxy-5-bromomethyl-2',3'-dideoxyuridine

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

A solution of 5′-O-TBDMS-3′-deoxythymidine (2) (700 mg, 2.055 mmol) in CCl4 (50 mL) was treated with NBS (702 mg, 4.11 mmol), followed by irradiation from a flood lamp (150 W) under reflux for 3 h to give (3). After filtering the solid, the filtrate was evaporated to dryness, followed by coevaporating with THF (20 mL×3). To a stirred solution of the 3-(trifluoroacetamido)prop-1-yne (620 mg, 4.11 mmol), DBU (0.61 mL, 4.11 mmol) and CuI (782 mg, 4.11 mmol) in THF (20 mL) was added a solution of 3 (Need conc. and solvent), followed by stirring at r.t for 15 h. After evaporating solvent, the residue was purified by silica gel column chromatography with MeOH:CH2Cl2 (0-4%) to afford 17 (170 mg, 0.35 mmol, 17%) over two steps. 1H NMR (CDCl3), 300 MHz) δ 9.55 (br s, 1H, NH), 7.74 (s, 1H, H6), 7.18 (br s, 1H, NH), 6.04 (dd, 1H, H1′, J=3.9 and 6.3 Hz), 4.23-4.10 (m, 3H, H4′ and CH2), 3.94 (dd, 1H, H5′, J=3.3 and 11.4 Hz), 3.75 (dd, 1H, H5′, J=3.6 and 11.4 Hz), 3.26-3.22 (m, 2H, 2 CH2), 2.45-2.35 (m, 1H, H2′), 2.09-1.85 (m, 3H, H2′, 2H3′), 0.90 (d, 9H, 3 CH3), 0.09 (s, 6H, 2 CH3). 19F NMR (CDCl3, 282.2 MHz) δ −76.22 (s, CF3).

Workup

  1. customfollowed by irradiation from a flood lamp (150 W)
  2. temperatureunder reflux for 3 h

Sources & evidence

ORD record
ord-3ce40a937ced47509dcefb9eed222b89
Source dataset
uspto-grants-2014_09
Patent number
US08835625B2

Reaction notes

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