Sodium Bicarbonate → Naphthalen-2-ylmethyl 3-fluoro-4-oxopiperidine-1-carboxylate

HRID 1095686Notes

Reaction equation

HRID 1095686 reaction equation
Cl.[F:2][CH:3]1[C:8](=[O:9])[CH2:7][CH2:6][NH:5][CH2:4]1.C([O-])(O)=O.[Na+].[C:15](Cl)(=[O:28])[O:16][CH2:17][C:18]1[CH:27]=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=1>C1COCC1.O>[F:2][CH:3]1[C:8](=[O:9])[CH2:7][CH2:6][N:5]([C:15]([O:16][CH2:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)=[O:28])[CH2:4]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 15764399(Naphthalen-2-yl)methyl carbonochloridateHCID 252105103-Fluoropiperidin-4-one hydrochloride

Product 1

HCID 66782177Naphthalen-2-ylmethyl 3-fluoro-4-oxopiperidine-1-carboxylateYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 3-fluoropiperidin-4-one hydrochloride (35.66 g, 232.2 mmol) in THF (800 mL) at 0° C. was added a solution of NaHCO3 (46.81 g, 557.3 mmol) in water (800 mL). After most of the bubbling had subsided the ensuing solution was treated with a solution of naphthalen-2-ylmethyl carbonochloridate (56.36 g, 255.4 mmol) in THF (300 mL) dropwise, over 30 minutes. The mixture was allowed to warm to ambient temperature over 16 hours with vigorous stirring. The mixture was diluted with water and extracted with EtOAc. The combined organic phases were washed with brine, then dried over Na2SO4, filtered arid concentrated. The residue was triturated with methanol and the resulting solid was filtered and dried in vacuo to afford 41.8 g (60%) of desired product as a cream-colored powder.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic phases were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered arid concentrated
  5. customThe residue was triturated with methanol
  6. filtrationthe resulting solid was filtered
  7. customdried in vacuo

Sources & evidence

ORD record
ord-1194c27dd7d74a8aa378bb923577d634
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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