反応 #1057259

反応方程式

Sodium cyanoborohydride

indoline

acetic acid

formaldehyde

→

N-methyl indoline

溶媒

methanol

反応条件

後処理

1. 1
   温度was cooled to 0° C. again
2. 2
   workup.STIRRINGThe mixture was stirred at room temperature under nitrogen for 3 h
3. 3
   その他quenched with 2 N NaOH
4. 4
   抽出extracted (3×) with methylene chloride
5. 5
   洗浄The combined organic layers were washed with brine
6. 6
   乾燥dried over Na2SO4
7. 7
   ろ過filtered
8. 8
   濃縮concentrated in vacuo
9. 9
   その他The residue was purified by chromatography (SiO2, EtOAc/methanol, 10:1)

実験手順

To a solution of the resulting indoline (180 mg, 0.603 mmol) and acetic acid (0.1 mL) in methanol (5 mL), 37% aqueous formaldehyde (0.054 mL, 0.723 mmol) was added dropwise at 0° C. The reaction mixture was stirred at room temperature under nitrogen for 1 h, and then was cooled to 0° C. again. Sodium cyanoborohydride (95 mg, 1.5 mmol) was added in portions at 0° C. The mixture was stirred at room temperature under nitrogen for 3 h and then quenched with 2 N NaOH and extracted (3×) with methylene chloride. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by chromatography (SiO2, EtOAc/methanol, 10:1) to afford the N-methyl indoline product, Example 53 as a white solid (140 mg, 74%): mp 63-65° C.; 1H NMR (300 MHz, CDCl3) δ 7.07-7.20 (m, 4H), 6.59 (d, J=8.0 Hz, 1H), 6.28 (d, J=8.0 Hz, 1H), 4.14 (t, J=7.9, 5.0 Hz, 1H), 3.58 (d, J=15.0 Hz, 1H), 3.46 (d, J=15.0 Hz, 1H), 3.33 (t, J=8.2 Hz, 2H), 2.93 (dd, J=11.3, 5.0 Hz, 1H), 2.82 (t, J=8.2 Hz, 2H), 2.72 (s, 3H), 2.54 (dd, J=11.3, 7.9 Hz, 1H), 2.42 (s, 3H); CI MS m/z 313 [C19H21ClN2+H]+; IR (KBr) 2940, 2796, 1611, 1594, 1489, 1372, 1286 cm−1; Anal. Calcd for C19H21ClN2: C, 72.95; H, 6.77; N, 8.95. Found: C, 72.70; H, 6.83; N, 8.78.

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