Potassium Carbonate → Methyl 6-chloro-2-(3-fluorophenethylamino)nicotinate

HRID 2080272Notes

Reaction equation

HRID 2080272 reaction equation
Cl[C:2]1[N:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[CH2:17][CH2:18][NH2:19].C([O-])([O-])=O.[K+].[K+].CN1C(=O)CCC1>C(OCC)(=O)C>[Cl:12][C:10]1[CH:9]=[CH:8][C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([NH:19][CH2:18][CH2:17][C:16]2[CH:20]=[CH:21][CH:22]=[C:14]([F:13])[CH:15]=2)[N:11]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 5339282-(3-Fluorophenyl)ethanamineHCID 11106516Methyl 2,6-dichloropyridine-3-carboxylate

Product 1

HCID 57542459Methyl 6-chloro-2-(3-fluorophenethylamino)nicotinateYield 54.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 2,6-dichloronicotinate (53.3 g, 0.26 mol), 3-fluorophenethyl amine (37.3 mL, 0.29 mol), K2CO3 (72 g 0.52 mol) and NMP (150 mL) was stirred at 100° C. for 10 hrs. The mixture was diluted with ethyl acetate (2×300 mL) and washed with brine. The organic layers were combined, dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography using hexane-EtOAc (9:1) as eluant to give methyl 6-chloro-2-(3-fluorophenethylamino)nicotinate as an off-white solid (44 g, 54%). LRMS (M+H+) m/z 309.0.

Workup

  1. washwashed with brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-3854c1a5424541b1b5272a2417167bb6
Source dataset
uspto-grants-2011_04
Patent number
US07932270B2

Reaction notes

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