Triphenylphosphine → 1-[4-(7-Chloro-1-methoxy-isoquinolin-6-yloxy)-1-trifluoromethyl-cyclohexyl]-propylamine

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Reaction Conditions

Reaction Steps

790 mg (3.51 mmol) of 4-(1-Amino-propyl)-4-trifluoromethyl-cyclohexanol (74) were dissolved using 8.0 ml of anhydrous THF. 1.20 g (4.56 mmol) of triphenylphosphin, 0.58 ml (3.51 mmol) of N,N-diisopropylethylamine, and 735 mg (3.51 mmol) of 7-chloro1-methoxy-isoquinolin-6-ol (81) were added and the mixture cooled to 0° C. At this temperature, 0.83 ml (5.26 mmol) of diethyl azodicarboxylate were added and the mixture stirred for 16 h at ambient temperature. Afterwards, the mixture was diluted with 20 ml of CH2Cl2 and washed successively with 20 ml of a 1N aqueous solution of NaOH, with 20 ml of a saturated aqueous solution of NH4Cl, using 20 ml of water, and with 20 ml of a saturated aqueous solution of NaCl, respectively. The organic layer was then treated with 20 ml of a 1N aqueous solution of HCl. Crude product precipitated, was filtered off and resuspended in 20 ml of a 1N aqueous solution of NaOH. This suspension was extracted three times using 20 ml of CH2Cl2. The organic layer was then dried using MgSO4 and evaporated. Chromatography of the residue on silica gel using t.-butylmethyl ether/n-heptane 1:1+1% acetic acid yielded 160 mg of the desired product as its acetate. Rt=0.79 min (Method P). Detected mass: 417.2 (M+H+).

Provenance & Evidence