Triethylamine → HCID 86731569, compound

HRID 1430584Notes

Reaction equation

HRID 1430584 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]#[C:9][C@@H:10]2[CH2:15][CH2:14][C@@H:13]([CH3:16])[N:12](CC3C=CC(OC)=CC=3)[CH2:11]2)=[N:6][CH:7]=1.C(N(CC)CC)C.ClC(OC(Cl)C)=O.ClC(OCCCl)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]#[C:9][C@@H:10]2[CH2:15][CH2:14][C@@H:13]([CH3:16])[NH:12][CH2:11]2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 123052-Chloroethyl chloroformateHCID 5213051-Chloroethyl chloroformateHCID 86731570HCID 86731570, compound

Product 1

HCID 86731569HCID 86731569, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-fluoro-2-{[(3S,6R)-1-(4-methoxybenzyl)-6-methylpiperidin-3-yl]ethynyl}pyridine (276 mg, 0.82 mmol) and triethylamine (0.23 mL, 1.6 mmol) in CH2Cl2 (5 mL) was cooled at 0° C. and treated with 1-chloroethyl chloroformate (0.18 mL, 1.6 mmol) and allowed to warm to ambient temperature. After stirring overnight, additional triethylamine (0.20 mL) and chloroethyl chloroformate (0.15 mL) was added and the reaction stirred overnight again. The reaction was quenched by addition of 1N NaOH. The layers were separated and the aqueous phase was extracted with CH2Cl2. The organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was taken up in MeOH and heated at reflux for 2 h. The reaction was concentrated in vacuo. The crude material was purified by silica gel flash chromatography eluting with 0-10% MeOH in CH2Cl2 to provide 5-fluoro-2-{[(3S,6R)-6-methylpiperidin-3-yl]ethynyl}pyridine as an orange solid which gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 219.3 for M+H+.

Workup

  1. stirringthe reaction stirred overnight again
  2. customThe reaction was quenched by addition of 1N NaOH
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with CH2Cl2
  5. washThe organics were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. temperatureheated
  10. temperatureat reflux for 2 h
  11. concentrationThe reaction was concentrated in vacuo
  12. customThe crude material was purified by silica gel flash chromatography
  13. washeluting with 0-10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-04605f9afd944db2885c9ecd00965fd4
Source dataset
uspto-grants-2015_01
Patent number
US08940898B2

Reaction notes

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