Water → N-methyl-N-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetra-hydro-2H-pyran-4-yl}methyl)ethanamine

HRID 272943ノート

反応式

HRID 272943 の反応式
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH3:7][N:8]([CH2:12][C:13]1([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:21][CH:20]=2)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:9](=O)[CH3:10].O.[OH-].[Na+]>O1CCCC1>[NH3:8].[CH3:7][N:8]([CH2:12][C:13]1([C:19]2[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:23][CH:24]=2)[CH2:14][CH2:15][O:16][CH2:17][CH2:18]1)[CH2:9][CH3:10]

参加物

7

反応物 4

HCID 962Water2 回HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 59837426HCID 59837426、化合物

生成物 2

HCID 222AmmoniaHCID 11653402N-methyl-N-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetra-hydro-2H-pyran-4-yl}methyl)ethanamine収率 105.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of LiAlH4 (1.0M in diethylether, 1.20 mL, 0.60 mmol) was added dropwise at 0° C. to a solution of N-methyl-N-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-acetamide (220 mg, 0.60 mmol) in tetrahydrofuran (1 mL) under an atmosphere of nitrogen. The reaction mixture was allowed to warm to ambient temperature overnight. The reaction mixture was cooled to 0° C., water (1 mL) was added dropwise followed by sodium hydroxide (2.0M, 3 mL) and water (1 mL). The resulting solid was filtered over a small pad of celite, washed with DCM (150 mL) and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 97.5:2.5:0.25 to 95.5:4.5:0.45 to give the title compound as a pale yellow oil (114 mg, 88%). 1H NMR (400 MHz, CDCl3) δ 7.18 (d, 2H), 6.86 (d, 2H), 4.04 (t, 2H), 3.78-3.70 (m, 2H), 3.52 (dt, 2H), 2.66 (t, 2H), 2.52-2.66 (m, 4H), 2.38 (s, 2H), 2.18 (quartet, 2H), 2.00-2.12 (m, 4H), 1.92-1.86 (m, 5H), 1.82-1.76 (m, 4H), 0.86 (t, 3H); HRMS (ESI+) 361.2850 (M+H)+.

後処理

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. filtrationThe resulting solid was filtered over a small pad of celite
  3. washwashed with DCM (150 mL)
  4. concentrationconcentrated in vacuo
  5. customThe compound was purified by column chromatography on Biotage® silica gel
  6. washeluting with dichloromethane

出典と根拠

ORDレコード
ord-1778b4b1c2c44786be99a89779987f38
出典データセット
uspto-grants-2008_11
特許番号
US07456164B2

反応ノート

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