Tetrahydrofuran → [3-Fluoro-4-(morpholin-4-yl)phenyl]methanamine

HRID 1446528Notes

Reaction equation

HRID 1446528 reaction equation
C1COCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)[C:16]#[N:17].[OH-].[Na+]>C(OCC)(=O)C.O>[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)[CH2:16][NH2:17]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 14798Sodium HydroxideHCID 11223033-Fluoro-4-(morpholin-4-yl)benzonitrileHCID 21226445Aluminium lithium hydride

Product 1

HCID 11572017[3-Fluoro-4-(morpholin-4-yl)phenyl]methanamineYield 80.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a THF (30 mL) suspension of lithium aluminum hydride (975 mg), a THF (10 mL) solution of 3-fluoro-4-(morpholin-4-yl)benzonitrile (4.41 g) was added dropwise at −78° C. Then, the reaction solution was allowed to be warmed to room temperature and agitated overnight. The reaction solution was cooled to 0° C. after confirming disappearance of the starting materials, water and 5N sodium hydroxide solution, and also ethyl acetate were added to the reaction solution one by one, and the organic layer was partitioned. After the obtained organic layer was washed with a saturated saline solution, it was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent:ethyl acetate=1:1→heptane-ethyl acetate), and 3.60 g of the title compound was obtained. The physical properties of the compound are as follows.

Workup

  1. temperatureThe reaction solution was cooled to 0° C.
  2. customthe organic layer was partitioned
  3. washAfter the obtained organic layer was washed with a saturated saline solution, it
  4. dry with materialwas dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent:ethyl acetate=1:1→heptane-ethyl acetate)

Sources & evidence

ORD record
ord-2544499f7e1c4c7da0f0f6f072c85b8c
Source dataset
uspto-grants-2010_02
Patent number
US07667041B2

Reaction notes

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