Trifluoroacetic acid → (4-(3-((R)-1-(2,4-dichlorophenyl)ethylamino)-4-fluorophenyl)piperazin-1-yl)((R)-piperidin-2-yl)methanone

HRID 75135Notes

Reaction equation

HRID 75135 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C@H:16]([NH:18][C:19]1[CH:20]=[C:21]([N:26]2[CH2:31][CH2:30][N:29]([C:32]([C@H:34]3[CH2:39][CH2:38][CH2:37][CH2:36][N:35]3C(OC(C)(C)C)=O)=[O:33])[CH2:28][CH2:27]2)[CH:22]=[CH:23][C:24]=1[F:25])[CH3:17]>ClCCl>[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C@H:16]([NH:18][C:19]1[CH:20]=[C:21]([N:26]2[CH2:27][CH2:28][N:29]([C:32]([C@H:34]3[CH2:39][CH2:38][CH2:37][CH2:36][NH:35]3)=[O:33])[CH2:30][CH2:31]2)[CH:22]=[CH:23][C:24]=1[F:25])[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689052HCID 86689052, compound

Product 1

HCID 71582713(4-(3-((R)-1-(2,4-dichlorophenyl)ethylamino)-4-fluorophenyl)piperazin-1-yl)((R)-piperidin-2-yl)methanoneYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1.5 mL) was added to a solution (R)-t-butyl 2-(4-(3-((R)-1-(2,4-dichlorophenyl)ethylamino)-4-fluorophenyl)piperazine-1-carbonyl)piperidine-1-carboxylate (0.080 g, 0.14 mmol) in dichloromethane (5 mL) at room temperature, and the solution was stirred for 1 h. Excess solvent was removed in vacuo, and the residue was diluted with dichloromethane. The organic layer was neutralized with aqueous saturated sodium bicarbonate solution, and the aqueous layer was further extracted with dichloromethane. The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo to give the title compound as a white solid (0.042 g, 0.088 mmol, 64%). 1H NMR (400 MHz, DMSO-d6) δ 9.25 (s, 1H), 8.60-8.55 (m, 1H), 7.56 (dd, J=8.4, 8.4 Hz, 2H), 7.38 (dd, J=2.4, 8.4 Hz, 1H), 6.92 (dd, J=9.2, 11.2 Hz, 1H), 6.26-6.09 (m, 3H), 4.83 (dd, J=6.4, 13.6 Hz, 1H), 4.37 (t, J=11.2 Hz, 1H), 3.76-3.48 (m, 4H), 3.21 (d, J=11.2 Hz, 1H), 3.09-3.05 (m, 2H), 2.90-2.84 (m, 2H), 1.95 (d, J=13.6 Hz, 1H), 1.73-1.60 (m, 3H), 1.45 (d, J=6.8 Hz, 3H); MS: (ES) m/z calculated for C24H30Cl2FN4O [M+H]+479.2. found 479.4.

Workup

  1. customExcess solvent was removed in vacuo
  2. additionthe residue was diluted with dichloromethane
  3. extractionthe aqueous layer was further extracted with dichloromethane
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a4ed2e3e129c48f886d415656f3b5538
Source dataset
uspto-grants-2014_09
Patent number
US08835419B2

Reaction notes

Loading…