تفاعل #338825

معادلة التفاعل

6-chloro-3-chloromethyl-4-cyclopentyloxy-2-methyl-pyridine hydrochloride salt

(S)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine

N,N-diisopropylethylamine

→

(S)-(6-chloro-4-cyclopentyloxy-2-methyl-pyridin-3-ylmethyl)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine

المذيبات

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction is cooled to ambient temperature
2. 2
   تركيزconcentrated in vacuo
3. 3
   workup.DISSOLUTIONThe obtained residue is dissolved in a mixture of hexane and ethyl:acetate (4:1, 100 mL)
4. 4
   ترشيحfiltered over a small pad of silica gel (35 g), which
5. 5
   غسيلis subsequently rinsed with additional 100 mL of the same mixture of hexane and ethyl acetate
6. 6
   تركيزThe filtered solution is concentrated in vacuo
7. 7
   أخرىthe resultant residue is chromatographed on silica gel (hexane/ethyl Acetate 4:1)

الإجراء التجريبي

A mixture of 6-chloro-3-chloromethyl-4-cyclopentyloxy-2-methyl-pyridine hydrochloride salt, (S)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine (3.0 g, 18.6 mmol), N,N-diisopropylethylamine (4.0 mL, 22.9 mmol), and anhydrous acetonitrile (50 mL) is stirred for 5 hours at 80° C. The reaction is cooled to ambient temperature and concentrated in vacuo. The obtained residue is dissolved in a mixture of hexane and ethyl:acetate (4:1, 100 mL) and filtered over a small pad of silica gel (35 g), which is subsequently rinsed with additional 100 mL of the same mixture of hexane and ethyl acetate. The filtered solution is concentrated in vacuo and the resultant residue is chromatographed on silica gel (hexane/ethyl Acetate 4:1) to afford (S)-(6-chloro-4-cyclopentyloxy-2-methyl-pyridin-3-ylmethyl)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine. 1H NMR: (CDCl3) 7.53 (m, 1H), 7.09 (m, 2H), 7.02 (m, 1H), 6.63 (s, 1H), 4.77 (m, 1H), 3.83 (d, 1H), 3.73 (dd, 1H), 3.56 (d, 1H), 2.73 (m, 2H), 2.63 (s, 3H), 2.07 (m, 2H), 2.04 (s, 3H), 1.98 (m, 2H), 1.82 (m, 4H), 1.68 (m, 4H).

المصدر