Ethyl orthoformate → Allyl 3-(methylamino)benzoate

HRID 1824613Notes

Reaction equation

HRID 1824613 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][CH:13]=1)[C:5]([O:7][CH2:8][CH:9]=[CH2:10])=[O:6].[CH:14](OCC)(OCC)OCC>FC(F)(F)C(O)=O>[CH3:14][NH:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][CH:13]=1)[C:5]([O:7][CH2:8][CH:9]=[CH2:10])=[O:6]

Participants

4

Reactant 2

HCID 31214Ethyl orthoformateHCID 18930599Allyl 3-aminobenzoate

Product 1

HCID 22168609Allyl 3-(methylamino)benzoateYield 17%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidCatalyst

Procedure

Allyl 3-aminobenzoate (5 g, 28.2 mM) was dissolved in triethyl orthoformate (50 ml) and trifluoroacetic acid (5 drops) was added. The solution was stirred and refluxed up through 3å molecular sieves for 5 hours. Solvent was removed, and the residue dissolved in ethanol (50 ml), followed by the addition of acetic acid (8.08 ml) and sodium cyanoborohydride (6.85 g, 0.108 M) in several portions. The mixture was stirred at ambient temperature for 16 hours, and solvent removed. The residue was dissolved in diethyl ether, washed with water, brine, and dried over MgSO4. Crude product was purified by chromatography on silica, eluting with a gradient from dichloromethane to dichloromethane/ethyl acetate (95:5), to give allyl 3-methylaminobenzoate (0.93 g, 17%). Nmr (CDCl3): δ 2.88 (s, 3H); 4.81 (dt, 2H); 5.23-5.45 (m, 2H); 5.94-6.13 (m, 1H); 6.83 (dd, 1H); 7.25 (dd, 1H); 7.33 (t, 1H); 7.43 (dm, 1H).

Workup

  1. temperaturerefluxed up through 3å molecular sieves for 5 hours
  2. customSolvent was removed
  3. dissolutionthe residue dissolved in ethanol (50 ml)
  4. additionfollowed by the addition of acetic acid (8.08 ml) and sodium cyanoborohydride (6.85 g, 0.108 M) in several portions
  5. stirringThe mixture was stirred at ambient temperature for 16 hours
  6. customsolvent removed
  7. dissolutionThe residue was dissolved in diethyl ether
  8. washwashed with water, brine
  9. dry with materialdried over MgSO4
  10. customCrude product was purified by chromatography on silica
  11. washeluting with a gradient from dichloromethane to dichloromethane/ethyl acetate (95:5)

Sources & evidence

ORD record
ord-c7ba42c478104d45a3ec540e56996885
Source dataset
uspto-grants-2006_05
Patent number
US07041836B2

Reaction notes

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