Sulfuric Acid → Methyl 4-acetamido-3,6-dichloro-5-fluoropicolinate

HRID 541040

反応式

HRID 541040 の反応式
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[Cl:14].C(Cl)(Cl)Cl.S(=O)(=O)(O)O.[C:24](OC(=O)C)(=[O:26])[CH3:25]>C1(C)C=CC=CC=1>[C:24]([NH:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[Cl:14])(=[O:26])[CH3:25]

参加物

6

反応物 4

HCID 1118Sulfuric AcidHCID 6212ChloroformHCID 7918Acetic AnhydrideHCID 22677265Methyl 4-amino-3,6-dichloro-5-fluoropicolinate

生成物 1

HCID 86709862Methyl 4-acetamido-3,6-dichloro-5-fluoropicolinate

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

実験手順

In a 50 mL three-neck round-bottomed flask was charged the methyl 4-amino-3,6-dichloro-5-fluoropicolinate (12.1 mmol), toluene (50 mL), and CHCl3 (15 mL). To this suspension was added dropwise a premixed solution of sulfuric acid (0.05 mmol) and acetic anhydride (24.2 mmol), in toluene (5 mL). The reaction mixture was then heated, under a N2 stream, to 55-60° C. and the reaction was monitored by TLC. Once the reaction was deemed complete the heating mantle was removed and the reaction solution was cooled to ambient temperature. The mixture was then added dropwise to a mixture of saturated aqueous NaHCO3/toluene/CHCl3 (180 mL, 3/10/5), stirred for 20 min, and the layers separated using a reparatory funnel. To the organic layer was added silica gel (14.8 g) and the solvent was removed using a rotary evaporator. The crude product on silica was then purified using a Combi-Flash silica gel purification system using ethyl acetate and hexane as eluents. The purity of the product was analyzed by HPLC: mp=183-186° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.5 (s, 1H, NH), 3.93 (s, 3H), 2.17 (s, 3H); 13C NMR (100.6 MHz, DMSO-d6) δ 167.9, 162.8, 151.7, 149.0, 142.8 (d, JF-C=24 Hz), 136.2 (d, JF-C=80 Hz), 134.7 (d, JF-C=56 Hz), 126.6, 53.2, 22.5; 19F NMR (376.5 MHz, DMSO-d6) δ −114.5; MS Calcd. for C9H7Cl2FN2O3: 280.0. Found: 281 (MH+), 245, 180.

後処理

  1. temperatureThe reaction mixture was then heated, under a N2 stream
  2. customto 55-60° C.
  3. customwas removed
  4. additionThe mixture was then added dropwise to a mixture of saturated aqueous NaHCO3/toluene/CHCl3 (180 mL, 3/10/5)
  5. customthe layers separated
  6. additionTo the organic layer was added silica gel (14.8 g)
  7. customthe solvent was removed
  8. customa rotary evaporator
  9. customThe crude product on silica was then purified
  10. customa Combi-Flash silica gel purification system

出典と根拠

ORDレコード
ord-4ce8f79f898b45cb98e1170852666dcc
出典データセット
uspto-grants-2014_10
特許番号
US08871943B2

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