Sulfuric Acid → 4-(Phenylamino)-1-(phenylmethyl)-4-piperidinecarboxamide

HRID 402329Notes

Reaction equation

[C:1]1([NH:7][C:8]2([C:21]#[N:22])[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)[OH:24].[OH-].[NH4+]>FC(F)(F)C(O)=O>[C:1]1([NH:7][C:8]2([C:21]([NH2:22])=[O:24])[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

Conditions

Temperature: 47.5 °C

Procedure

Aminonitrile 1 (2.0 g, 6.86 mmol) was dissolved in 11 mL of trifluoroacetic acid under a nitrogen atmosphere. Sulfuric acid (2.7 mL) was added dropwise. The light brown solution was stirred at 45-50° C. for 16 h. The reaction mixture was cooled to room temperature and slowly poured into an ammonium hydroxide 40 mL/ice mixture. The solution was filtered and the solids were collected to give 1.73 g of amide 2 in an 82% yield. mp 179-182° C.; 1H NMR (CDCl3) δ 7.33-7.16 (m, 5H), 6.89 (br s, 1H), 6.78 (t, 1H, J=7.33 Hz), 6.63 (d, 2H, J=7.33 Hz), 5.48 (s, 1H), 4.05 (s, 1H), 2.77-2.71 (m, 2H), 2.37-2.30 (m, 2H), 2.10 (t, 2H, J=11.91 Hz), 1.95 (br d, 2H, J=13.28 Hz); 13C NMR (CDCl3) 178.7, 143.8, 138.3, 129.3, 129.1, 129.0, 128.3, 127.2, 119.3, 116.2, 63.1, 58.3, 48.8, 31.4.

Workup

temperatureThe reaction mixture was cooled to room temperature
filtrationThe solution was filtered
customthe solids were collected

Sources & evidence

ORD record: ord-b1a89b153b3b407485020d7044e2eef2
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08742111B1

Reaction notes

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