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

HRID 1804519노트

반응식

HRID 1804519 반응식
[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]

참가 물질

5

반응물 3

HCID 443297Hydroxyamine hydrochloride2회HCID 516892Sodium Bicarbonate2회HCID 67456438Tert-butyl 1-(4-cyano-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate

생성물 1

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

시약·촉매·용매 1

HCID 3776Isopropanol용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-2def0f3048b142a5ac81580f513f332a
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354398B2

반응 노트

불러오는 중…