1,5-Diazabicyclo(4.3.0)non-5-ene → 1-(3-O-Acetyl-2,5-dideoxy-beta-L-glycero-pent-4-enofuranosyl)-thymine
Reaction equation
[C:1]([O:4][C@H:5]1[C@@H:9]([CH2:10]I)[O:8][C@@H:7]([N:12]2[CH:20]=[C:18]([CH3:19])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:6]1)(=[O:3])[CH3:2].C1CN2C(=NCCC2)C1>CC#N>[C:1]([O:4][C@H:5]1[C:9](=[CH2:10])[O:8][C@H:7]([N:12]2[CH:20]=[C:18]([CH3:19])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:6]1)(=[O:3])[CH3:2]Participants
Procedure
To an CH3CN (40 mL) solution of 7 (5.5 g, 13.95 mmol) was added DBN (6.9 mL, 55.81 mmol) at 0° C., and the reaction mixture was stirred at room temperature for 17 h. After neutralization with AcOH, the reaction mixture was evaporated to dryness. The residue was partitioned between CHCl3/saturated aqueous NaHCO3 (200 mL×3/50 mL). Silica gel column chromatography (hexane/EtOAc=2/1-1/1) of the organic layer gave 8 (3.34 g, 90%) as a foam: 1H NMR (CDCl3) δ: 1.96 (3H, d, J6,Me=1.3 Hz, Me), 2.06 (3H, s, Ac), 2.21 (1H, dt, Jgem=15.2 Hz, J1′,2′a=J2′a,3′=2.7 Hz, H-2′a), 2.83 (1H, dt, Jgem=15.2 Hz, J1′,2′b=J2′b,3′=7.1 Hz, H-2′b), 4.51 (1H, dd, Jgem=2.4 Hz, J3′,5′a=0.8 Hz, H-5′a), 4.73 (1H, dd, Jgem=2.4 Hz and J3′,5′b=0.7 Hz, H-5′b), 5.70-5.73 (1H, m, H-3′), 6.44 (1H, dd, J1′,2′a=2.7 Hz and J1′,2′b=7.1 Hz, H-1′), 7.25 (1H, d, J6,Me=1.3 Hz, H-6), 8.54 (1H, br, NH); FAB-MS m/z 267(M++H).
Workup
- customAfter neutralization with AcOH, the reaction mixture was evaporated to dryness
- customThe residue was partitioned between CHCl3/saturated aqueous NaHCO3 (200 mL×3/50 mL)
Sources & evidence
- ORD record
- ord-0a1ab878bcde4e149d0d9b7f1e6dd799
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09126971B2
Reaction notes
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