Green and environment-friendly preparation method of tenofovir

[0029] Compound I is The molar ratio of compound I to potassium carbonate is 1:5; the molar ratio of compound I to dimethyl hydroxymethylphosphonate is 1:5; the molar ratio of compound I to diethyl azodicarboxylate is 1:1.5 ; The molar ratio of compound I and triphenylphosphine is 1:1.5; the molar ratio of compound I and sodium hydroxide is 1:1.5.

[0030] Specific steps are as follows:

[0031] Step (1), the compound I (102g), S-propylene carbonate (149g), potassium carbonate (690g) aqueous solution was dissolved in the organic solvent dimethylformamide, reacted at 100 ° C for 4h, cooled to room temperature, reduced Concentrate the system under pressure to obtain intermediate II; the hydrogen spectrum of intermediate II: 1 H-NMR (600MHz, DMSO-d 6 )δ H :10.51(s,1H),8.59(s,1H),8.19(s,1H),8.05(s,1H),3.90(m,2H),3.70(d,J=8.8Hz,1H),1.16( d, J=8.8Hz, 3H).

[0032] Step (2), dissolve intermediate II, dimethyl hydroxymethylphosphonate (700g) and triphenylphosphine (393.5g) in d...

[0035] Compound I is The mol ratio of compound I and potassium bicarbonate is 1:5; The mol ratio of compound I and diethyl hydroxymethyl phosphonate is 1:5; The mol ratio of compound I and two p-chlorobenzyl azodicarboxylates is 1:1.5; the molar ratio of compound I to trimethylphosphine is 1:1.5; the molar ratio of compound I to lithium hydroxide is 1:1.5.

[0036] Specific steps are as follows:

[0037] In step (1), compound I (149g), S-propylene carbonate (102g), and potassium bicarbonate (500g) were dissolved in toluene, an organic solvent, reacted at 110°C for 5h, cooled to room temperature, and concentrated under reduced pressure to obtain Intermediate II; hydrogen spectrum data of intermediate II; 1 H-NMR (600MHz, DMSO-d 6 )δ H :10.61(s,1H),8.63(s,1H),8.03(s,1H),3.90(m,2H),3.68(d,J=8.6Hz,1H),2.14(s,3H),1.15( d, J=8.6Hz, 3H).

[0038] Step (2), dissolve intermediate II, diethyl hydroxymethylphosphonate (700g) and trimethylphosphine (114g) in toluene, stir at room t...