Trifluoroacetic acid → 4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]piperidine-4-carbonitrile

HRID 273024Notes

Reaction equation

HRID 273024 reaction equation
[C:1]([C:3]1([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:18][CH:17]=2)[CH2:8][CH2:7][N:6](C(OC(C)(C)C)=O)[CH2:5][CH2:4]1)#[N:2].FC(F)(F)C(O)=O>ClCCl>[N:26]1([CH2:25][CH2:24][CH2:23][O:22][C:19]2[CH:20]=[CH:21][C:16]([C:3]3([C:1]#[N:2])[CH2:4][CH2:5][NH:6][CH2:7][CH2:8]3)=[CH:17][CH:18]=2)[CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 68578770Tert-butyl 4-cyano-4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]piperidine-1-carboxylate

Product 1

HCID 598373684-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]piperidine-4-carbonitrileYield 115.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-cyano-4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]piperidine-1-carboxylate (500 mg, 1.24 mmol) was stirred for 1 hour in trifluoroacetic acid (1.91 ml, 24.8 mmol) and dichloromethane (30 ml). More trifluoroacetic acid (3 ml) was added and the reaction stirred at room temperature for another hour. The reaction mixture was quenched with saturated aqueous sodium carbonate solution (15 ml) and the layers separated. The organic layer was dried over sodium sulphate and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 to 90:10:1 by volume) to provide the title compound (450 mg, 18% over 2 steps). 1H NMR (400 MHz, CD3OD) δ 1.81-1.85 (m, 4H), 1.91-2.09 (m, 6H), 2.59-2.62 (m, 4H), 2.69 (t, 2H), 2.99 (t, 2H), 3.12-3.15 (m, 2H), 4.04 (t, 2H), 6.96 (d, 2H), 7.42 (d, 2H). HRMS ESI+ m/z 314.2227 [MH]+.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium carbonate solution (15 ml)
  2. customthe layers separated
  3. dry with materialThe organic layer was dried over sodium sulphate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 to 90:10:1 by volume)

Sources & evidence

ORD record
ord-7648bfeb279b49c583439b777b94bbbf
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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