Tetrabutylammonium Fluoride → Lamivudine

To a solution of the β anomer 17 (0.15 g, 0.32 mmol) in THF (25 mL) was added tetrabutylammonium fluoride 1M in THF (0.35 mL, 0.35 mmol, 1.1 eq) and the reaction was allowed to stir at room temperature until TLC indicated the disappearance of starting material (30 min). The reaction mixture was concentrated under reduced pressure and the residue purified by preparative TLC using 12% MeOH/CHCl3 as development solvent to give 0.055 g (75%) of 3 from ethyl ether/MeOH (trace) as a white crystalline solid. [α]23D =-121.6 (c 1.1, MeOH) (for the S,R isomer 2 [α]23D =120.96 (c 1.06, MeOH)); 1H NMR: ((CD3)2SO) δ 3.03 (dd, J5,4a =4.4 Hz, J4a,4b =11.86 Hz, 1 H, 4a-H), 3.43 (dd, J5,4b =5.3 Hz, J4a,4b =11.86 Hz, 1 H, 4b-H), 3.80 (app t on D2O exchange goes to d, J2,2-CH2-OR =4.17 Hz, 2 H, 2-CH2 -OH), 5.27 (t, J2-CH2,OH =4.6 Hz, 1 H, 2-CH2OH), 5.22 (t, J2,2-CH2-OH =4.17 Hz, 1 H, 2-H), 5.88 (d, J5,6 =7.47 Hz, 1 H, H-5), 6.21 (app t, J=5.05 and 4.84 Hz, 1 H, 5-H), 7.19 (bs, 2 H, NH2), 7.89 (d, J5,6 =7.47 Hz, 1 H, H-6).

1. customthe disappearance of starting material (30 min)
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. customthe residue purified by preparative TLC

ORD-Eintrag

ord-9dd9e53838e64349bfafd944e71e35ae

Quelldatensatz

uspto-grants-1993_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05248776