Benzaldehyde → (R)-N-(1-(naphthalen-1-yl)ethyl)-3-(m-tolyl)propan-1-amine

反応式

[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[N:10]1C[CH2:13][CH2:12][C:11]1=O.BrCCC[C:20]1[CH:25]=[CH:24][CH:23]=[C:22](C)C=1.[CH3:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]>>[CH3:1][C:2]1[CH:7]=[C:6]([CH2:13][CH2:12][CH2:11][NH:10][C@@H:28]([C:29]2[C:22]3[C:33](=[CH:20][CH:25]=[CH:24][CH:23]=3)[CH:32]=[CH:31][CH:30]=2)[CH3:27])[CH:5]=[CH:4][CH:3]=1

参加物

反応物 4

HCID 240Benzaldehyde

HCID 8900Heptane

HCID 13387N-methyl-2-pyrrolidone

HCID 218898661-(3-Bromopropyl)-3-methylbenzene

生成物 1

HCID 53696875(R)-N-(1-(naphthalen-1-yl)ethyl)-3-(m-tolyl)propan-1-amine

反応条件

温度: 27.5 °C

実験手順

To a stirred solution of (1R)-1-naphthyl ethylamine (2, 10 g, 0.058 mol) was added the benzaldehyde (3, 17.04 g, 0.058 mol) and stirred at 25-30° C. for 1-2 h. After completion of the reaction (by HPLC) N-methyl-2-pyrrolidinone (30 mL) was added to the mixture and stirred for 15-20 min followed by addition of 1-(3-bromopropyl)-3-methylbenzene (18.68 g, 0.087 mol). The temperature of reaction mass was raised to 125-130° C. and maintained until completion of the reaction (by HPLC). The reaction mass was quenched with water (100 mL), pH of the resulting solution was adjusted to 8-9 using aqueous ammonia, and the solution was extracted with toluene (100 mL). The toluene layer was separated, washed with water (100 mL) followed by 10% sodium metabisulphite (100 mL×2). Water (100 mL) was added into toluene layer, and the pH of the solution was adjusted to 0.5-1.5 using concentrated hydrochloric acid. The resulting solution was stirred, and the layers were separated. The organic layer was washed with water (100 mL×2) and concentrated under reduced pressure to provide thick syrup. Syrup was dissolved in n-heptane (60 mL) and stirred for 2 h, and the solid obtained was filtered. The wet solid was suspended in ethyl acetate (50 mL); the solution was heated at 55-60° C. for 30 min, cooled to 15-20° C., filtered, washed with ethyl acetate, and dried to afford des(trifluorocinacalcet), the title compound, as a white crystalline solid. Yield: 11.0 g (55.92%); HPLC purity: 99.60%; Chiral Purity: 99.90%; IR (KBr) cm−1: 3435, 3006, 2962, 2945, 2798, 1588, 1455, 799, 771, 702; MS: m/z=304.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6): δ=1.66-1.68 (d, 3H), 1.93-1.96 (m, 2H), 2.22 (s, 3H), 2.52-2.54 (m, 2H), 2.71-2.74 (dt, 1H), 2.90-2.94 (dt, 1H), 5.29-5.31 (q, 1H), 6.89-6.97 (dd, J=8.0 Hz and 3.0 Hz, 3H), 7.11-7.13 (t, J=8.0 Hz, 1H), 7.59-7.63 (dd, J=8.0 Hz and 3.0 Hz, 3H), 7.97-8.02 (m, 3H), 8.23-8.25 (d, J=8.0 Hz, 1H), 9.24 (bs, 1H), 9.84 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ=20.13 (CH3), 21.02 (CH3), 27.16 (CH2), 31.92 (CH2), 44.88 (CH2), 52.07 (CH), 122.68, 124.51, 125.25, 125.62, 126.19, 126.64, 126.98, 128.64, 128.89, 130.36, 133.39, 134.22, 137.36, 140.59.