Hydrochloric Acid → 1-(Thiazol-4-yl)cyclopropanamine

HRID 1628233

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HRID 1628233 반응식
[S:1]1[CH:5]=[C:4]([C:6]#[N:7])[N:3]=[CH:2]1.[CH2:8]([Mg]Br)[CH3:9].B(F)(F)F.CCOCC.Cl.[OH-].[Na+]>CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].CCOCC.C1(C)C=CC=CC=1>[S:1]1[CH:5]=[C:4]([C:6]2([NH2:7])[CH2:9][CH2:8]2)[N:3]=[CH:2]1

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 8000Boron trifluoride etherateHCID 14798Sodium HydroxideHCID 150694-CyanothiazoleHCID 178418443HCID 178418443, 화합물

생성물 1

HCID 552856761-(Thiazol-4-yl)cyclopropanamine수율 49.3%

시약·촉매·용매 3

HCID 11026Titanium isopropoxide촉매HCID 1140Toluene용매HCID 3283Diethyl Ether용매2회

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온도
-70 °C

실험 절차

Thiazole-4-carbonitrile (1035 mg, 9397 μmol) was azeotroped with toluene. Et2O was added, and the clear solution was cooled to −70° C., followed by addition of titanium tetraisopropoxide (3025 μl, 10337 μmol), and ethylmagnesium bromide (6265 μl, 18795 μmol). The reaction mixture turned yellow. It remained yellow until about 15 min. The reaction was raised to RT, the solution changed into black. After 1 h., boron trifluoride diethyl etherate (2361 μl, 18795 μmol) was added and stirred for 1.5 hr. Then 1N HCl 27 mL was added, followed by 100 mL ether, 95 mL 10% NaOH. The reaction was extracted with Et2O×2 and 30% IPA/CHCl3×1. The organic layer was concentrated and purified with silica gel chromatography using 0-10% MeOH/DCM. 650 mg of product 14.2.B was obtained in 49% yield.

후처리

  1. temperatureThe reaction was raised to RT
  2. waitAfter 1 h.
  3. extractionThe reaction was extracted with Et2O×2 and 30% IPA/CHCl3×1
  4. concentrationThe organic layer was concentrated
  5. custompurified with silica gel chromatography

출처 및 근거

ORD 기록
ord-ae043e8723ad458a9b60ddee57e3eb51
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785468B2

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