Hydrochloric Acid → 1-[5-(2,2-Dimethyl-propyl)-isoxazol-3-yl]-cyclopropylamine

HRID 1664234Notes

Reaction equation

HRID 1664234 reaction equation
[CH3:1][C:2]([CH3:12])([CH3:11])[CH2:3][C:4]1[O:8][N:7]=[C:6]([C:9]#[N:10])[CH:5]=1.[CH2:13]([Mg]Br)[CH3:14].Cl.[OH-].[Na+]>C(OCC)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:1][C:2]([CH3:12])([CH3:11])[CH2:3][C:4]1[O:8][N:7]=[C:6]([C:9]2([NH2:10])[CH2:14][CH2:13]2)[CH:5]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 666495545-(2,2-Dimethyl-propyl)isoxazole-3-carbonitrileHCID 178418443HCID 178418443, compound

Product 1

HCID 674401081-[5-(2,2-Dimethyl-propyl)-isoxazol-3-yl]-cyclopropylamine

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

To a mixture of 5 g (30.4 mmol) of 5-(2,2-dimethyl-propyl)-isoxazole-3-carbonitrile and 10.1 ml (34.1 mmol) of titanium(IV) isopropoxide in 150 ml of dry diethyl ether a solution of 22 ml of ethylmagnesium bromide (3 M in diethyl ether, 66.0 mmol) is added at −70° C. The reaction mixture is allowed to reach rt within two hours, 7.6 ml (60.6 mmol) of boron trifluoride-diethyl etherate are added and stirring is continued for one hour. After addition of 90 ml of 1M aq hydrochloric acid and 450 ml of diethyl ether two clear phases are obtained which are treated with 300 ml of 10% aq sodium hydroxide. The aqueous phase is extracted with diethyl ether, the combined organic phases are dried over sodium sulfate and evaporated to afford a dark orange oil. After filtration over a C18-bond elut column (Varian) with THF/MeCN the oil is purified by HPLC (dissolved in 6 ml of tetrahydrofuran, 25 injections, XBridge C18 column, 19×150 mm, 5 μM, gradient of 95% MeCN in water to 10% MeCN in water, containing 0.02% of ammonium hydroxide). The combined product fractions are concentrated and the product is extracted with DCM to yield the product as an orange solid.

Workup

  1. additionis added at −70° C
  2. waitis continued for one hour
  3. customare obtained which
  4. extractionThe aqueous phase is extracted with diethyl ether
  5. dry with materialthe combined organic phases are dried over sodium sulfate
  6. customevaporated
  7. customto afford a dark orange oil
  8. filtrationAfter filtration over a C18-bond elut column (Varian) with THF/MeCN the oil
  9. customis purified by HPLC (dissolved in 6 ml of tetrahydrofuran, 25 injections, XBridge C18 column, 19×150 mm, 5 μM, gradient of 95% MeCN in water to 10% MeCN in water, containing 0.02% of ammonium hydroxide)
  10. concentrationThe combined product fractions are concentrated
  11. extractionthe product is extracted with DCM

Sources & evidence

ORD record
ord-f69ffaf7ecad42d485f2fee50cbbec5d
Source dataset
uspto-grants-2011_10
Patent number
US08039455B2

Reaction notes

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