Acetic Acid → HCID 961624, compound

HRID 1822181Notes

Reaction equation

HRID 1822181 reaction equation
[CH2:1](NC1C=CC=CC=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(O)=O.[BH3-]C#N.[Na+].[Cl:23][C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][C:30]=1[F:31])[NH2:27]>CO>[CH2:1]([NH:27][C:26]1[CH:28]=[CH:29][C:30]([F:31])=[C:24]([Cl:23])[CH:25]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 97083-Chloro-4-fluoroanilineHCID 66028BenzylanilineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 961624HCID 961624, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

Benzylaniline (3.69 g, 34.8 mmol), AcOH (1.11 mL), and NaBH3CN were added to a solution of 3-chloro-4-fluoroaniline (5.07 g, 34.8 mmol) in MeOH (200 mL) containing molecular sieves. The resulting mixture was stirred at 23° C. for 18 h. Sieves were removed by filtration and the filtrate was concentrated. The residue was partitioned between saturated aqueous sodium bicarbonate solution (100 mL) and CH2Cl2 (50 mL, 2×20 mL). The combined organic extracts were dried over MgSO4 and concentrated. The residue was purified by flash column chromatography (SiO2, 0-12% EtOAc/hexanes gradient) to give N-benzyl-3-chloro 4-fluoroaniline (7-1) 1H NMR (300 MHz, CDCl3) δ 7.36-7.25 (m, 5H), 6.93 (dd, J=8.8, 5.8 Hz, 1H), 6.62 (dd, J=6.1, 3.1 Hz, 1H), 6.44 (ddd, J=8.9, 3.7, 3.1 Hz, 1H), 4.27 (s, 2H), 3.98 (brs, 1H).

Workup

  1. additioncontaining molecular sieves
  2. customSieves were removed by filtration
  3. concentrationthe filtrate was concentrated
  4. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution (100 mL) and CH2Cl2 (50 mL, 2×20 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (SiO2, 0-12% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-d056ed9ef3a249ebb23dfc879ec0ed46
Source dataset
uspto-grants-2009_10
Patent number
US07608739B2

Reaction notes

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