Aluminium lithium hydride → 1-[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine

HRID 17048Notes

Reaction equation

HRID 17048 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH3:23])=[C:8]([C:10]2[C:11]([C:20]#[N:21])=[CH:12][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:15]=2)[CH:9]=1)([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>CCOCC>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH3:23])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:12][C:11]=2[CH2:20][NH2:21])[CH:9]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 533636455'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-carbonitrile

Product 1

HCID 591351271-[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

5′-Isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carbonitrile (996.2 mg, 3.12 mmol) was dissolved in Et2O (33 mL) and cooled to 0° C. LAH (12.49 mL of a 1 M solution in Et2O, 12.49 mmol) was added dropwise by syringe. After stirring at 0° C. for 10 minutes, the reaction was warmed to room temperature and stirred at room temperature for 6 hours. The reaction was then quenched by slow dropwise addition of 1.5 mL of H2O (vigorous evolution of gas), followed by 1.5 mL of 30% NaOH, followed by 3.0 mL of H2O. The resulting gelatinous precipitate was washed with 5×20 mL of CH2Cl2; the organic washes were dried over Na2SO4, filtered and concentrated. Purification of the residue by flash chromatography with 2% MeOH/CH2Cl2 containing 0.1% Et3N afforded 1-[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine. Rf=0.30 (10% MeOH/CH2Cl2). LCMS=324.3 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.77 (s, 1H), 7.55 (d, J=6.8 Hz, 1H), 7.32 (d, J=7.8 Hz, 1H), 7.25 (dd, J=8.3, 2.1 Hz, 1H), 7.00 (d, J=2.1 Hz, 1H), 6.92 (d, J=8.4 Hz, 1H), 3.66-3.74 (m, 5H), 2.91 (m, 1H), 1.26 (d, J=6.9 Hz, 6H).

Workup

  1. temperaturethe reaction was warmed to room temperature
  2. stirringstirred at room temperature for 6 hours
  3. customThe reaction was then quenched by slow dropwise addition of 1.5 mL of H2O (vigorous evolution of gas)
  4. washThe resulting gelatinous precipitate was washed with 5×20 mL of CH2Cl2
  5. dry with materialthe organic washes were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by flash chromatography with 2% MeOH/CH2Cl2 containing 0.1% Et3N

Sources & evidence

ORD record
ord-ff04c61311af49c0bd41bfe39713234e
Source dataset
uspto-grants-2010_06
Patent number
US07737295B2

Reaction notes

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