反应 #2150368

反应方程式

3-(N-acetyl) amino-4-methoxybenzoic acid

nitric acid

3-amino-4-methoxybenzoic acid

HCl

→

2-nitro-4-methoxy-5 (N-acetyl)aminobenzoic acid

收率 72.0%

溶剂

反应条件

后处理

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGThe reaction mixture was stirred for 2 hours at room temperature
3. 3
   过滤the precipitate was filtered off
4. 4
   洗涤washed with 3×10 ml of 0.1N HCl and 5×10 ml water
5. 5
   其他to produce 5.97 g (about 95%)
6. 6
   workup.STIRRINGThe solution was stirred at 0° C. for an additional hour
7. 7
   过滤Precipitate was filtered off
8. 8
   洗涤washed with 5×20 mls of water
9. 9
   其他dried

实验过程

3-amino-4-methoxybenzoic acid (“19”) (Aldrich Chemical; Milwaukee, Wis.) (5 g or 29.9 mmol) was suspended in 40 ml acetic acid. Acetic anhydride (3 ml or 1:04 eq) was added by stirring. The reaction mixture was stirred for 2 hours at room temperature. 25 ml of 0.1N HCl was added and the precipitate was filtered off and washed with 3×10 ml of 0.1N HCl and 5×10 ml water to produce 5.97 g (about 95%). 3-(N-acetyl) amino-4-methoxybenzoic acid (“20”) (5 g or 23.5 mmol) was added to 20 ml of fuming nitric acid at 0° C. on vigorous stirring. The solution was stirred at 0° C. for an additional hour and poured onto 200 g of ice. Precipitate was filtered off, washed with 5×20 mls of water and dried to produce 4.38 g (about 72%) of 2-nitro-4-methoxy-5 (N-acetyl)aminobenzoic acid (“21”), which was converted into 2-nitro-4-methoxy-5-(N-acetyl)aminoacetophenone (“22”) (about 63% yield) as described. 2-nitro-4-methoxy-5-(N-acetyl)aminoacetophenone (“22”) (1 g or 4.76 mmol) was dissolved in 5 ml of DMF and the solution was added to 5-biotinamidocaproyl chloride prepared separately from 5-biotinamidocaproic acid (1.55 g or 1 eq.) and 5 ml thionyl chloride. The reaction mixture was stirred overnight at room temperature and added to 100 ml of diethyl ether. Precipitate was purified using small silica gel column and a step gradient of MeOH in CHCl3 to give 1.16 g (about 47%) of 2-nitro-4-methoxy-5-(5-biotinamidocaproamido) acetophenone (“23”). This intermediate was converted into its corresponding alcohol (about 85% yield) and into the reactive NHS ester derivative 5-(5-biotinamidocaproamido)-4-methoxy-1-(2-nitro)phenylethyl-N-hydroxysuccinimidyl carbonate (“25”) with about a 69% yield.

来源