Sodium borohydride → 2-(3,4,5-Trifluorophenyl)piperidine

HRID 473795Notes

Reaction equation

HRID 473795 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]([C:8]1[CH:13]=[C:12]([F:14])[C:11]([F:15])=[C:10]([F:16])[CH:9]=1)=O.[BH4-].[Na+]>O1CCCC1.CO>[F:16][C:10]1[CH:9]=[C:8]([CH:6]2[CH2:5][CH2:4][CH2:3][CH2:2][NH:1]2)[CH:13]=[C:12]([F:14])[C:11]=1[F:15]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 675060535-Amino-1-(3,4,5-trifluorophenyl)pentan-1-one

Product 1

HCID 644600202-(3,4,5-Trifluorophenyl)piperidineYield 677.6%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To 5-amino-1-(3,4,5-trifluorophenyl)pentan-1-one (0.11 g, 0.48 mmol) in tetrahydrofuran/methanol 4:1 (10 mL) was added in portions over 20 minutes solid sodium borohydride (0.20 g, 5.0 mmol) and stirring was continued 18 hours at 25° C. The reaction mixture was concentrated then taken into ethyl acetate (40 mL), washed with saturated sodium chloride/2 N aqueous sodium hydroxide 10:1 (11 mL) then dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes, 1:1) to give 2-(3,4,5-trifluorophenyl)piperidine (0.70 g, 68% yield) as an oil. 1H NMR (400 MHz, CDCl3): 7.01 (m, 2H), 3.52 (m, 1H), 3.17 (m, 1H) 2.77 (m, 1H), 2.07 (br s, 1H), 1.88 (m, 1H), 1.74 (m, 1H), 1.64 (m, 1H), 1.55-1.35 (m, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washwashed with saturated sodium chloride/2 N aqueous sodium hydroxide 10:1 (11 mL)
  3. dry with materialthen dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexanes, 1:1)

Sources & evidence

ORD record
ord-01dc9dbad1ff4d49bd75820f2c232dad
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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