Tetrahydrofuran → Methyl 2,4,5-triamino-3-fluorobenzoate

HRID 571031Notes

Reaction equation

HRID 571031 reaction equation
[NH2:1][C:2]1[C:11]([F:12])=[C:10]([NH2:13])[C:9]([N+:14]([O-])=O)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].O1CCCC1>CO.[Pd]>[NH2:1][C:2]1[C:11]([F:12])=[C:10]([NH2:13])[C:9]([NH2:14])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

5

Reactant 2

HCID 8028TetrahydrofuranHCID 59365494Methyl 2,4-diamino-3-fluoro-5-nitrobenzoate

Product 1

HCID 59365495Methyl 2,4,5-triamino-3-fluorobenzoateYield 108.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of methyl 2,4-diamino-3-fluoro-5-nitrobenzoate (5) (40.0 g, 173.7 mmol) and 5% Pd/C (3.0 g, Type 487; 0.4 mol % Pd relative to starting material), in methanol (300.0 mL) and tetrahydrofuran (300.0 mL) was stirred at 2000 RPM, under hydrogen (−3.5 bar), at 50° C. in a 1.5 L hydrogenation vessel. After 6 hours the vessel was purged with nitrogen and HPLC analysis indicated that no starting material remained. The mixture was then filtered under nitrogen pressure and the filter washed through with THF (160 mL), to give a clear yellow solution. The solvent was removed by rotary evaporation, to provide methyl 2,4,5-triamino-3-fluorobenzoate (9) 37.5 g (93.3% w/w by NMR) as a solid, yield ˜100%. 1H NMR (400 MHz, d6 DMSO) δ 3.69 (3H, s, NMe), 4.20 (2H, br s, NH2), 5.24 (2H, br s, NH2), 5.70 (2H, br s, NH2), 6.83 (1H, d, J 1, Ar—H). 13C NMR (100 MHz, d6 DMSO) δ 51 (CH3), 98 (C, d, J 5), 110 (CH, d, J 2), 125 (C, d, J 6), 131 (C, d, J 12), 133 (C, d, J 12), 139 (CF, d, J 225), 166 (C═O). νmax/cm−1 3480, 3461, 3373, 3356, 3280, 3163, 1679, 1655, 1314. MS APCI (+) m/z 200 (M+1) detected.

Workup

  1. customAfter 6 hours the vessel was purged with nitrogen and HPLC analysis
  2. filtrationThe mixture was then filtered under nitrogen pressure
  3. washthe filter washed through with THF (160 mL)
  4. customto give a clear yellow solution
  5. customThe solvent was removed by rotary evaporation

Sources & evidence

ORD record
ord-a5f140a8cd7448d89b1524ee73a7c16e
Source dataset
uspto-grants-2015_05
Patent number
US09024040B2

Reaction notes

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