تفاعل #992740

معادلة التفاعل

lithium triethylborohydride

hydrogen peroxide

Acetic acid

hydrogen peroxide

sodium metabisulfite

3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxylic acid methyl ester

→

title compound

المردود 73.0%

6-hydroxymethyl-4H-pyrido[3,2-b][1,4]thiazin-3-one

المردود 73.0%

المذيبات

THF

MeOH

THF

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwas added over 35 min
2. 2
   تركيزThe reaction mixture was concentrated under reduced pressure at 50° C. whereupon the product
3. 3
   أخرىto crystallize
4. 4
   workup.ADDITIONMeOH was added to the suspension in three portions (3×180 mL)
5. 5
   أخرىfollowed by removal of ca. 180 mL of solvent under reduced pressure
6. 6
   workup.ADDITIONafter each addition
7. 7
   ترشيحThe solid was filtered
8. 8
   غسيلwashed with water (2×150 mL) and tert-butyl methyl ether (150 ml)
9. 9
   workup.ADDITIONTo the wet cake was added toluene in two portions (2×50 mL)
10. 10
    أخرىfollowed by the removal of 50 mL solvent under reduced pressure at 50° C

الإجراء التجريبي

To a suspension of 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxylic acid methyl ester (WO 02/056882; 36.0 g, 161 mmol) in THF (240 mL) was added a solution of lithium triethylborohydride in THF (1M, 430 g, 3 eq.) at 5-10° C. over 70 min. Acetic acid (87 g, 9 eq.) was added dropwise at 10-25° C. to the brown solution. MeOH (180 mL) was added to the suspension at 20° C. The reaction vessel was then constantly cooled externally at 21-37° C. while a 5% w/w hydrogen peroxide solution (300 mL, 3 eq.) was added over 35 min, and a 10% w/w hydrogen peroxide solution (300 mL, 6 eq.) was added over further 35 min. A sat. aq sodium metabisulfite solution (147 g) was added at 24-36° C. The reaction mixture was concentrated under reduced pressure at 50° C. whereupon the product started to crystallize. MeOH was added to the suspension in three portions (3×180 mL) followed by removal of ca. 180 mL of solvent under reduced pressure after each addition. The solid was filtered, washed with water (2×150 mL) and tert-butyl methyl ether (150 ml). To the wet cake was added toluene in two portions (2×50 mL) followed by the removal of 50 mL solvent under reduced pressure at 50° C. The title compound was obtained as a light yellow solid (22.86 g, 73% yield; m.p. 120-135° C.).

المصدر