Methyl 6-chloropyridine-3-carboxylate → HCID 10520108, compound

HRID 1274126Notes

Reaction equation

HRID 1274126 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.Cl[C:16]1[CH:21]=[CH:20][C:19]([C:22]([O:24][CH3:25])=[O:23])=[CH:18][N:17]=1>CN(C=O)C>[CH3:25][O:24][C:22](=[O:23])[C:19]1[CH:20]=[CH:21][C:16]([NH:1][CH:2]2[CH2:7][CH2:6][N:5]([CH2:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH2:4][CH2:3]2)=[N:17][CH:18]=1

Participants

4

Reactant 2

HCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 4158521-Benzyl-4-piperidylamine

Product 1

HCID 10520108HCID 10520108, compoundYield 45.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

4-Amino-1-benzylpiperidine (30 mL, 150 mmol) and N,N'-diisopropylethyl amine (25 mL, 150 mmol) were added sequentially to a solution of methyl 2-chloropyridine-5-carboxylate (5 g, 29.1 mmol) in DMF (20 mL) at 25° C. The mixture was stirred at 75° C. for 12 h. The reaction mixture was then evaporated and diluted with a mixture of sat. NaCl (aq)/EtOAc (100 mL, v/v, 50:50). The aqueous layer was extracted with more EtOAc (3×50 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuc to give a yellow oily residue. Purification of the residue by flash column chromatography (gradient elution 70 to 80% EtOAc/hexanes) provided the title compound (4.3 g, 45.4%): TLC (Rf =0.20; 60% EtOAc/hexanes); 1H NMR (CDCl3) δ 8.73 (d, 1H, J=2.1), 7.95 (m, 1H), 7.30 (m, 5H), 6.32 (d, 1H, J=8.8), 5.01 (d, 1H, J=7.8), 3.85 (s, 3H), 3.71 (m, 1H), 3.52 (s, 2H), 2.85 (m, 2H), 2.18 (m, 2H), 1.20 (m, 2H), 1.57 (m, 2H); 13C NMR (CDCl3) δ 166.4, 160.1, 151.6, 138.3, 129.0, 128.1, 127.6, 127.0, 115.0, 105.8, 63.0, 52.0, 51.4, 48.4, 32.3; HRMS (FAR) m/z 326.1879 (M+H)+ (C19H23N3O2 requires 326.1869).

Workup

  1. customThe reaction mixture was then evaporated
  2. additiondiluted with a mixture of sat. NaCl (aq)/EtOAc (100 mL, v/v, 50:50)
  3. extractionThe aqueous layer was extracted with more EtOAc (3×50 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuc
  7. customto give a yellow oily residue
  8. customPurification of the residue
  9. washby flash column chromatography (gradient elution 70 to 80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-945344ee0ea04858ab7212c765017ae5
Source dataset
uspto-grants-2000_12
Patent number
US06156758

Reaction notes

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