Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1) → 4-(4-Fluorophenyl)-3-carboxyethylpiperidine

HRID 2296767Notes

Reaction equation

HRID 2296767 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=O)[NH:11][CH2:10][CH:9]2[CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:4][CH:3]=1.F[B-](F)(F)F.C[O+](C)C.[BH4-].[Na+]>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH:9]2[CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 4311764Sodium borohydrideHCID 227338414-(4-Fluorophenyl)-3-carboxyethylpiperidin-6-one

Product 1

HCID 544207614-(4-Fluorophenyl)-3-carboxyethylpiperidineYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
16 °C

Procedure

4-(4-fluorophenyl)-3-carboxyethylpiperidin-6-one (12.0 g, 0.045 mol, trans/cis-ratio˜1:1) was added in one portion to a solution of trimethyloxonium fluoroborate (12.0 g, 0.081 mol) in dichloromethane (80 ml) and the resulting solution stirred, at 14-18° C., for 60 hours under an argon atmosphere. The solvent was removed in vacuo, and then the residue was dissolved in absolute ethanol (100 ml), heated to 45° C. and treated with sodium borohydride (10.0 g, 0.26 mol) in 1.0 g portions, allowing the mixture to boil under reflux. Most of the solvent was evaporated and the residue quenched with water (60 ml) followed by concentrated hydrochloric acid. After neutralization with 10% sodium bicarbonate solution the products were extracted with dichloromethane (150 and 50 ml). The extracts were dried with anhydrous sodium sulphate, filtered, and evaporated to afford the title compound as a cis/trans mixture (1:1). Yield 75%. A portion of the product was purified by column chromatography (silica gel, eluted with ethyl acetate-triethylamine, 98:2).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in absolute ethanol (100 ml)
  3. temperatureheated to 45° C.
  4. temperatureunder reflux
  5. customMost of the solvent was evaporated
  6. customthe residue quenched with water (60 ml)
  7. extractionAfter neutralization with 10% sodium bicarbonate solution the products were extracted with dichloromethane (150 and 50 ml)
  8. dry with materialThe extracts were dried with anhydrous sodium sulphate
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-d03f406d90dc4cb28d281c9f76ea58bf
Source dataset
uspto-grants-2002_12
Patent number
US06489347B1

Reaction notes

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