2-Fluoropyridine → Benzyl 1-(pyridin-2-yl)piperidine-3-carboxylate

HRID 1696282Notes

Reaction equation

HRID 1696282 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:2]1.CCN(C(C)C)C(C)C.F[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1.C([O-])([O-])=O.[Na+].[Na+]>CO.N1C=CC=CC=1.C(O)(C)(C)C>[N:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:2]1

Participants

8

Reactant 4

HCID 97462-FluoropyridineHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 13419237Benzyl piperidine-3-carboxylate

Product 1

HCID 66845119Benzyl 1-(pyridin-2-yl)piperidine-3-carboxylate

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1049PyridineSolventHCID 6386tert-ButanolSolvent

Procedure

Pure benzyl piperidine-3-carboxylate (170 mg, 0.776 mmol; Example 31) was placed in a microwave tube. DIPEA (0.50 mL), tert-BuOH (1.5 mL) and 2-fluoropyridine (Aldrich, 0.40 mL) were added to the tube via syringes before the tube was subjected to microwave irradiation at 180° C. for 20 min. LC/MS showed partial conversion to the desired pyridine derivative. The tube was subjected to further microwave irradiation at 220° C. for 20 min and then it was allowed to cool to room temperature. The volatiles were removed by rotary evaporation to provide 229 mg of crude oil which was dissolved in MeOH (8.0 mL) and then subjected to reverse phase HPLC. The pure fractions were poured into Na2CO3 (10%, 75 mL) and extracted with EtOAc (3×50 mL), washed with brine (sat, 150 mL), dried with sodium sulfate, filtered and concentrated to provide 90 mg of benzyl 1-(pyridin-2-yl)piperidine-3-carboxylate. MS m/z: 297 (M+1)

Workup

  1. customirradiation at 180° C. for 20 min
  2. customThe tube was subjected to further microwave irradiation at 220° C. for 20 min
  3. customThe volatiles were removed by rotary evaporation
  4. customto provide 229 mg of crude oil which
  5. extractionextracted with EtOAc (3×50 mL)
  6. washwashed with brine (sat, 150 mL)
  7. dry with materialdried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-473d86c96a4f41608217558a6351876b
Source dataset
uspto-grants-2012_04
Patent number
US08163766B2

Reaction notes

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