Trifluoroacetic acid → N,N-dimethyl-1-(piperidin-4-yl)-2',3'-dihydrospiro[piperidine-4,4'-quinoline]-1'-carboxamide

HRID 2382990Notes

Reaction equation

HRID 2382990 reaction equation
[CH3:1][N:2]([CH3:33])[C:3]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]2([CH2:19][CH2:18][N:17]([CH:20]3[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]3)[CH2:16][CH2:15]2)[CH2:7][CH2:6]1)=[O:4].C(O)(C(F)(F)F)=O>ClCCl.C(#N)C>[CH3:1][N:2]([CH3:33])[C:3]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]2([CH2:15][CH2:16][N:17]([CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[CH2:18][CH2:19]2)[CH2:7][CH2:6]1)=[O:4]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57863245tert-butyl 4-(1'-(dimethylcarbamoyl)-2',3'-dihydro-1'H-spiro[piperidine-4,4'-quinoline]-1-yl)piperidine-1-carboxylate

Product 1

HCID 24798103N,N-dimethyl-1-(piperidin-4-yl)-2',3'-dihydrospiro[piperidine-4,4'-quinoline]-1'-carboxamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The tert-butyl 4-(1′-(dimethylcarbamoyl)-2′,3′-dihydro-1′H-spiro[piperidine-4,4′-quinoline]-1-yl)piperidine-1-carboxylate 2ad (1.34 g, 2.93 mmol) was dissolved in 40 mL anhydrous dichloromethane and cooled to 0° C. The rapidly stirring solution was treated with TFA (20 mL) and allowed to come to room temperature over 2 hours. The reaction was diluted with ˜20 mL acetonitrile and concentrated to an oil. The oil was brought up in 100 mL 1.0 N HCL and washed with diethyl ether (3×30 mL). The aqueous solution was then basified with 5 N NaOH and the product extracted into dichloromethane (3×50 mL). The organic layer was washed with brine (100 mL), dried over Na2SO4, filtered and concentrated to yield N,N-dimethyl-1-(piperidin-4-yl)-2′,3′-dihydrospiro[piperidine-4,4′-quinoline]-1′-carboxamide 2ae as a colorless oil. LC/MS (10-99% CH3CN/0.05% TFA gradient over 5 min): m/z 357.2, retention time 0.78 minutes. 1H NMR (400 MHz, DMSO-d6) δ 7.35 (d, J=7.8 Hz, 1H), 7.06 (t, J=7.3 Hz, 1H), 6.90 (t, J=7.5 Hz, 1H), 6.75 (d, J=8.0 Hz, 1H), 3.40 (t, J=5.8 Hz, 2H), 3.13 (d, J=12.4 Hz, 2H), 2.77 (s, 6H), 2.71-2.61 (m, 5H), 2.42 (t, J=10.8 Hz, 3H), 1.92 (t, J=10.7 Hz, 2H), 1.86-1.78 (m, 5H), 1.58-1.45 (m, 4H).

Workup

  1. concentrationconcentrated to an oil
  2. washwashed with diethyl ether (3×30 mL)
  3. extractionthe product extracted into dichloromethane (3×50 mL)
  4. washThe organic layer was washed with brine (100 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-42bd2721860340f5b201ddd435f44242
Source dataset
uspto-grants-2012_09
Patent number
US08263605B2

Reaction notes

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