Methanol → (4-Fluorobenzyl)isobutylamine

HRID 1403710Notes

Reaction equation

HRID 1403710 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH2:10]([NH2:14])[CH:11]([CH3:13])[CH3:12].[BH4-].[Na+].CO>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:14][CH2:10][CH:11]([CH3:13])[CH3:12])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6558IsobutylamineHCID 680234-FluorobenzaldehydeHCID 4311764Sodium borohydride

Product 1

HCID 966924(4-Fluorobenzyl)isobutylamineYield 76%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 4-fluorobenzaldehyde (6.0 mL, 55.93 mmol), and isobutylamine (3.72 g, 50.85 mmol) in toluene (30 mL) was heated at reflux using Dean-Stark apparatus of 5 hours. The mixture was stood at ambient temperature for 18 hours then cooled in an ice-bath. Sodium borohydride (2.89 g, 76.28 mmol) was added followed by MeOH (5 mL). After 1 hour at 0° C. the reaction was quenched with 1M HCl, basified with a saturated solution of NaHCO3 and extracted into EtOAc (3×). The combined extracts were washed with brine, dried over Na2SO4 and concentrated under vacuum. Purification by silica gel column chromatography (0-10% MeOH in DCM) afforded the title compound (6.98 g, 76%) as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 7.28 (m, 2H), 7.00 (m, 2H), 3.74 (s, 2H), 2.42 (d, J=6.8 Hz, 2H), 1.76 (m, 1H), 0.91 (d, J=6.6 Hz, 6H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux
  3. customDean-Stark apparatus of 5 hours
  4. temperaturethen cooled in an ice-bath
  5. customAfter 1 hour at 0° C. the reaction was quenched with 1M HCl
  6. extractionextracted into EtOAc (3×)
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under vacuum
  10. customPurification by silica gel column chromatography (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-4a6e0b06e40b4666879677be1b73c5f4
Source dataset
uspto-grants-2014_12
Patent number
US08912219B2

Reaction notes

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