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

HRID 1628233

Reaction equation

HRID 1628233 reaction equation
[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

Participants

9

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-70 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-ae043e8723ad458a9b60ddee57e3eb51
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Linked notes

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