Water → HCID 11494529, compound

HRID 272938Notes

Reaction equation

HRID 272938 reaction equation
[CH2:1]([N:3]([CH2:7][C:8]1([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][N:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)=[CH:16][CH:15]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)[C:4](=O)[CH3:5])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>O1CCCC1>[NH3:3].[CH2:1]([N:3]([CH2:7][C:8]1([C:14]2[CH:15]=[CH:16][C:17]([O:20][CH2:21][CH2:22][CH2:23][N:24]3[CH2:25][CH2:26][CH2:27][CH2:28]3)=[CH:18][CH:19]=2)[CH2:9][CH2:10][O:11][CH2:12][CH2:13]1)[CH2:4][CH3:5])[CH3:2]

Participants

7

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 23091680HCID 23091680, compound

Product 2

HCID 222AmmoniaHCID 11494529HCID 11494529, compoundYield 106.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-ethyl-N-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)acetamide (119 mg, 0.307 mmol) in tetrahydrofuran (1 mL) was added dropwise at 0° C. to a solution of LiAlH4 (1.0M in diethylether, 0.614 mL, 0.614 mmol) 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 (0.5 mL) was then added dropwise followed by sodium hydroxide (2.0M, 0.5 mL) and water (0.5 mL) again. The resulting solid was filtered over a small pad of celite, washed with DCM (100 mL) and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 94.5:5.5:0.55 to 91:9:0.9 to give the title compound as a pale yellow oil (61 mg, 53%). 1H NMR (400 MHz, CDCl3) δ 7.18 (d, 2H), 6.86 (d, 2H), 4.02 (t, 2H), 3.70-3.78 (m, 2H), 3.48 (dt, 2H), 2.64 (t, 2H), 2.58-2.46 (m, 4H), 2.38 (s, 2H), 2.20 (quartet, 4H), 2.13-1.96 (m, 4H), 1.92-1.86 (m, 2H), 1.82-1.78 (m, 4H), 0.82 (t, 6H); HRMS (ESI+) 375.3006 (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 (100 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-343bd8de2d124be2a74fa611f5c143fb
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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