Tetrabutylammonium Fluoride → Lamivudine

HRID 6424

Reaction equation

HRID 6424 reaction equation
C([CH:5]([O:19][SiH](C1C=CC=CC=1)C1C=CC=CC=1)[C@H:6]1[S:10][CH2:9][C@@H:8]([N:11]2[CH:18]=[CH:17][C:15]([NH2:16])=[N:14][C:12]2=[O:13])[O:7]1)CCC.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[OH:19][CH2:5][C@H:6]1[S:10][CH2:9][C@@H:8]([N:11]2[CH:18]=[CH:17][C:15]([NH2:16])=[N:14][C:12]2=[O:13])[O:7]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 131718191HCID 131718191, compound

Product 1

HCID 60825LamivudineYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-9dd9e53838e64349bfafd944e71e35ae
Source dataset
uspto-grants-1993_09
Patent number
US05248776

Linked notes

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