反応 #56695

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

実験手順

To a solution of the indoline product of Example 42 (110 mg, 0.420 mmol) and acetic acid (0.1 mL) in methanol (4 mL), 37% aqueous formaldehyde (0.04 mL, 0.5 mmol) was added dropwise at room temperature. The reaction mixture was stirred at room temperature under nitrogen for 1 h, and then sodium cyanoborohydride (66 mg, 1.05 mmol) was added in portions at room temperature. 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 41, as a white solid (92 mg, 80%): mp 88-90° C.; 1H NMR (500 MHz, CDCl3) δ7.17-7.28 (m, 5H), 6.59 (d, J=8.0 Hz, 1H), 6.26 (d, J=8.0 Hz, 1H), 4.17 (dd, J=8.5, 5.4 Hz, 1H), 3.62 (d, J=15.0 Hz, 1H), 3.43 (d, J=15.0 Hz, 1H), 3.31 (m, 2H), 2.96 (dd, J=11.3, 5.4 Hz, 1H), 2.82 (m, 2H), 2.70 (s, 3H), 2.54 (dd, J=11.3, 8.5 Hz, 1H), 2.42 (s, 3H); CI MS m/z=279 [C19H22N2+H]+; IR (KBr) 3020, 2940, 2773, 1610, 1487 cm−1; Anal. Calcd for C19H22N2-0.1 H2O: C, 81.45; H, 7.99; N, 10.00. Found: C, 81.21; H, 8.00; N, 9.74.

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