Hydroxyamine hydrochloride → tert-butyl 1-(4-(N'-hydroxycarbamimidoyl)-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate

HRID 1804519ノート

反応式

HRID 1804519 の反応式
[C:1]([C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[CH2:11][CH:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:5][C:4]=1[C:21]([F:24])([F:23])[F:22])#[N:2].Cl.[NH2:26][OH:27].C(=O)(O)[O-].[Na+]>C(O)(C)C>[OH:27][N:26]=[C:1]([C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[CH2:9][CH:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:11]2)=[CH:5][C:4]=1[C:21]([F:24])([F:23])[F:22])[NH2:2]

参加物

5

反応物 3

HCID 443297Hydroxyamine hydrochloride2 回HCID 516892Sodium Bicarbonate2 回HCID 67456438Tert-butyl 1-(4-cyano-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate

生成物 1

HCID 86659948tert-butyl 1-(4-(N'-hydroxycarbamimidoyl)-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate収率 88%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒2 回

実験手順

A solution of tert-butyl 1-(4-cyano-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate (0.268 g, 0.787 mmol), hydroxylamine hydrochloride (0.109 g, 1.57 mmol), and sodium bicarbonate (0.265 g, 3.15 mmol) in isopropanol (2.2 mL) was stirred at 90° C. for 6.0 hrs. HPLC and LCMS indicated that the reaction was 69% complete. Additional hydroxylamine hydrochloride (0.109 g), sodium bicarbonate (0.265 g), and isopropanol (2.2 mL) were added, and heating was continued for 16 hrs. The isopropanol was removed under reduced pressure, and the reaction mixture was diluted with ethyl acetate and washed with water (2×), washed with brine, and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate (0.258 g, 0.690 mmol, 88% yield) of a colorless, viscous oil. The compound had an HPLC ret. time=0.880 min.−Column: PHENOMENEX® S5 4.6×30 mm (2 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=374.10.

後処理

  1. temperatureheating
  2. customThe isopropanol was removed under reduced pressure
  3. additionthe reaction mixture was diluted with ethyl acetate
  4. washwashed with water (2×)
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationConcentration under reduced pressure

出典と根拠

ORDレコード
ord-2def0f3048b142a5ac81580f513f332a
出典データセット
uspto-grants-2013_01
特許番号
US08354398B2

反応ノート

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