Acetic Anhydride → N-(3-chloro-1H-pyrazol-4-yl)acetamide

HRID 705485ノート

反応式

HRID 705485 の反応式
Cl.[Cl:2][C:3]1[C:7]([NH2:8])=[CH:6][NH:5][N:4]=1.C(=O)(O)[O-].[Na+].[O:14]1CC[CH2:16][CH2:15]1.C(OC(=O)C)(=O)C>C(OCC)(=O)C.O.COC(C)(C)C>[Cl:2][C:3]1[C:7]([NH:8][C:15](=[O:14])[CH3:16])=[CH:6][NH:5][N:4]=1

参加物

8

反応物 4

HCID 7918Acetic AnhydrideHCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 178479102HCID 178479102、化合物

生成物 1

HCID 178474372N-(3-chloro-1H-pyrazol-4-yl)acetamide収率 83%

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒2 回HCID 15413tert-Butyl methyl ether溶媒

反応条件

温度
5 °C

実験手順

A 100-mL 3-neck round bottom flask was charged with 3-chloro-1H-pyrazol-4-amine.hydrochloride (5.00 g, 32.5 mmol) and water (25 mL). Sodium bicarbonate (10.9 g, 130 mmol) was added slowly over 10 minutes (off-gassing during addition), followed by tetrahydrofuran (25 mL). The mixture was cooled to 5° C. and acetic anhydride (3.48 g, 34.1 mmol) was added over 30 minutes while maintaining the internal temperature at <10° C. The reaction was stirred at 5° C. for 1 hour, at which point thin layer chromatography (TLC) analysis [Eluent: ethyl acetate (EtOAc)] indicated that the starting material had disappeared and a major product was exclusively formed. The reaction mixture was diluted with ethyl acetate (25 mL) and water (25 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×25 mL). The combined organic layers were concentrated to afford an off-white solid, which was suspended in methyl tert-butylether (MTBE, 20 mL), stirred for 1 hour, and filtered. The solid was rinsed with methyl tert-butylether (20 mL) and further dried under vacuum at room temperature (about 22° C.) for 4 hours to give a white solid (4.28 g, 83%): mp 162-164° C.; 1H NMR (400 MHz, DMSO-d6) δ 12.90 (bs, 1 H), 9.49 (s, 1 H), 7.97 (s, 1 H), 2.02 (s, 3 H); 13C NMR (101 MHz, DMSO-d6) δ 167.81, 130.07, 123.72, 116.73, 22.58; EIMS m/z 159 ([M]+).

後処理

  1. addition(off-gassing during addition)
  2. temperaturewhile maintaining the internal temperature at <10° C
  3. customa major product was exclusively formed
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×25 mL)
  6. concentrationThe combined organic layers were concentrated
  7. customto afford an off-white solid, which
  8. filtrationfiltered
  9. washThe solid was rinsed with methyl tert-butylether (20 mL)
  10. customfurther dried under vacuum at room temperature (about 22° C.) for 4 hours

出典と根拠

ORDレコード
ord-88d221d56b8743558299adda11c6882e
出典データセット
uspto-grants-2015_11
特許番号
US09174962B2

反応ノート

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