Acetic Acid → HCID 46938834, compound

HRID 1641296Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12]C[CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].[NH4+:23].[OH-].[C:25](O)(=O)[CH3:26]>>[CH2:1]([N:8]1[CH2:13][CH2:12][C:25]([NH:19][C:18]2[CH:20]=[CH:21][CH:22]=[C:16]([F:15])[CH:17]=2)([C:26]#[N:23])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Reactant 4

HCID 176Acetic Acid

HCID 97423-Fluoroaniline

HCID 14923Ammonium Hydroxide

HCID 51700761-Benzyl-2-piperidone

Product 1

HCID 46938834HCID 46938834, compound

Procedure

To a 0° C. solution of 15 g (79 mmol) N-benzyl piperidone in 80 mL acetic acid was added 7.6 mL (79 mmol) 3-fluoro aniline followed by dropwise addition of 10.5 mL (79 mmol) trimethylsilylnitrile (TMSCN). The reaction mixture was allowed to warm to rt and stirred for 1 hr, then poured onto a mixture of 120 g ice and 120 g concentrated NH4OH. The resulting mixture was extracted 2×300 mL CH2Cl2 and the combined extracts washed with brine, dried over MgSO4, filtered, and concentrated. The residue was suspended in 100 mL diisopropylether and stirred 30 min and filtered to give 1-benzyl-4-[(3-fluorophenyl)amino]piperidine-4-carbonitrile. 1H NMR (CDCl3, 400 MHz) δ 7.26-7.35 (m, 5H); 7.19 (app q, J=8.06 Hz, 1H); 6.55-6.66 (m, 3H); 3.78 (s, 1H); 3.56 (s, 2H); 2.80 (br m, 2H); 2.48 (ddd, J=12.5, 12.5, 2.2 Hz, 2H); 2.35 (ddd, J=13.4, 2.56, 2.56 Hz, 2H); 1.92 (ddd, J=13.2, 13.2, 3.1 Hz, 2H) High resolution mass spec (FT/ICR) calc M+H=310.1714 found 310.1749.

Workup

extractionThe resulting mixture was extracted 2×300 mL CH2Cl2
washthe combined extracts washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
stirringstirred 30 min
filtrationfiltered

Sources & evidence

ORD record: ord-37d64b7035e24ac7b2cb15eb7712f9ea
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08114887B2

Reaction notes

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