Trifluoroacetic acid → Ethyl 6-bromo-2-methyl-5-(pentan-3-ylamino)nicotinate

HRID 906184Notes

Reaction equation

HRID 906184 reaction equation
[NH2:1][C:2]1[C:3]([Br:14])=[N:4][C:5]([CH3:13])=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].[CH3:15][CH2:16][C:17](=O)[CH2:18][CH3:19].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].FC(F)(F)C(O)=O>C(OCC)(=O)C>[Br:14][C:3]1[C:2]([NH:1][CH:17]([CH2:18][CH3:19])[CH2:16][CH3:15])=[CH:12][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:5]([CH3:13])[N:4]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7288Ethyl ketoneHCID 5049666Sodium triacetoxyborohydride2×HCID 71464138Ethyl 5-amino-6-bromo-2-methylnicotinate

Product 1

HCID 86631951Ethyl 6-bromo-2-methyl-5-(pentan-3-ylamino)nicotinateYield 74.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl 5-amino-6-bromo-2-methylnicotinate (1.267 g, 4.89 mmol) in ethyl acetate (30 ml) were added 3-pentanone (0.463 g, 5.38 mmol), sodium triacetoxyborohydride (1.244 g, 5.868 mmol) and trifluoroacetic acid (1.15 g, 9.78 mmol) at room temperature. After stirring overnight at room temperature, another portion of sodium triacetoxyborohydride (0.6 g, 2.83 mmol) was added. The reaction mixture was stirred for another 6 hours. The reaction mixture was quenched with water (20 ml). The organic layer was washed with saturated sodium bicarbonate and brine. After evaporation of solvent, ethyl 6-bromo-2-methyl-5-(pentan-3-ylamino)nicotinate (1.20 g, 74.6% yield) was purified by column chromatography with 7% ethyl acetate/Hexane as eluent. 1H NMR (400 MHz, CDCl3): 7.35 (s, 1H), 4.40 (q, J=6.8 Hz, 2H), 4.10 (br, s, 1H), 3.30 (m, 1H), 2.68 (s, 3H), 1.8-1.5 (m, 4H), 1.42 (t, J=6.8 Hz, 3H), 1.0 (t, J=7.2 Hz, 6H). MS (EI) for C14H21BrN2O2: 329.1 (MH+).

Workup

  1. stirringThe reaction mixture was stirred for another 6 hours
  2. customThe reaction mixture was quenched with water (20 ml)
  3. washThe organic layer was washed with saturated sodium bicarbonate and brine

Sources & evidence

ORD record
ord-f956c7df660c41c1b49962e4b832fc8a
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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