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

HRID 272943Notes

Reaction equation

HRID 272943 reaction equation
[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]

Participants

7

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 59837426HCID 59837426, compound

Product 2

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-1778b4b1c2c44786be99a89779987f38
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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