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

HRID 402209

反応式

HRID 402209 の反応式
NC1C=C(C=CC=1OC)C(O)=O.Cl.[C:14]([NH:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=1[O:27][CH3:28])[C:21]([OH:23])=[O:22])(=[O:16])[CH3:15].[N+:29]([O-])([OH:31])=[O:30]>>[N+:29]([C:24]1[CH:25]=[C:26]([O:27][CH3:28])[C:18]([NH:17][C:14](=[O:16])[CH3:15])=[CH:19][C:20]=1[C:21]([OH:23])=[O:22])([O-:31])=[O:30]

参加物

5

反応物 4

HCID 313Hydrochloric AcidHCID 944Nitric AcidHCID 178233-Amino-4-methoxybenzoic acidHCID 36113063-Acetamido-4-methoxybenzoic acid

生成物 1

HCID 146684062-nitro-4-methoxy-5(N-acetyl)aminobenzoic acid収率 72%

実験手順

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)aminoacetophenoae (“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.

後処理

  1. additionwas added
  2. stirringThe reaction mixture was stirred for 2 hours at room temperature
  3. filtrationthe precipitate was filtered off
  4. washwashed with 3×10 ml of 0.1N HCl and 5×10 ml water
  5. customto produce 5.97 g (about 95%)
  6. stirringThe solution was stirred at 0° C. for an additional hour
  7. filtrationPrecipitate was filtered off
  8. washwashed with 5×20 mls of water
  9. customdried

出典と根拠

ORDレコード
ord-308bf89c029b4e9785fc0c08d4fe0aec
出典データセット
uspto-grants-2014_06
特許番号
US08742084B2

関連ノート

読み込み中…