3-(2-(Trifluoromethyl)phenyl)-2-propenoic acid → (E)-1-(6-methoxy-3,4-dihydro-2H-spiro[isoquinoline-1,4'-piperidine]-1'-yl)-3-(2-(trifluoromethyl)phenyl)prop-2-en-1-one

HRID 390163Notes

Reaction equation

HRID 390163 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:15](=[CH:16][CH:17]=1)[C:9]1([CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)[NH:8][CH2:7][CH2:6]2.[F:18][C:19]([F:32])([F:31])[C:20]1[CH:30]=[CH:29][CH:28]=[CH:27][C:21]=1[CH:22]=[CH:23][C:24](O)=[O:25].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:15](=[CH:16][CH:17]=1)[C:9]1([CH2:10][CH2:11][N:12]([C:24](=[O:25])/[CH:23]=[CH:22]/[C:21]3[CH:27]=[CH:28][CH:29]=[CH:30][C:20]=3[C:19]([F:31])([F:32])[F:18])[CH2:13][CH2:14]1)[NH:8][CH2:7][CH2:6]2

Participants

8

Reactant 5

HCID 749393-(2-(Trifluoromethyl)phenyl)-2-propenoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 210546866-methoxy-3,4-dihydro-2H-spiro[isoquinoline-1,4'-piperidine]

Product 1

HCID 44226870(E)-1-(6-methoxy-3,4-dihydro-2H-spiro[isoquinoline-1,4'-piperidine]-1'-yl)-3-(2-(trifluoromethyl)phenyl)prop-2-en-1-one

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 6-methoxy-3,4-dihydro-2H-spiro[isoquinoline-1,4′-piperidine] (570 mg, 2.45 mmol) in CH2Cl2 (20 mL) were added ortho-(trifluoromethyl)cinnamic acid (132 mg, 0.61 mmol), i-Pr2NEt (0.43 mL, 2.45 mmol), HOBt (99 mg, 0.73 mmol) and EDC.HCl (141 mg, 0.73 mmol). The mixture was stirred at rt for 3 d. The mixture was diluted with EtOAc (80 mL), washed with water (30 mL) and satd aq NaHCO3 (30 mL), and dried over Na2SO4. Removal of the solvent left an orange oil (378 mg). A portion of the oil was purified by preparative HPLC to afford (E)-1-(6-methoxy-3,4-dihydro-2H-spiro[isoquinoline-1,4′-piperidine]-1′-yl)-3-(2-(trifluoromethyl)phenyl)prop-2-en-1-one. LC-MS Method 1 tR=1.37, min, m/z=431; 1H NMR (CDCl3) 2.25 (m, 4H), 3.16 (br s, 2H), 3.39 (m, 1H), 3.45 (br s, 2H), 3.78 (s, 3H), 3.84 (m, 1H), 4.11 (m, 1H), 4.78 (m, 1H), 4.9 (1H), 6.65 (s, 1H), 6.83 (m, 2H), 7.12 (d, 1H), 7.4-7.75 (4H), 7.98 (d, 1H).

Workup

  1. washwashed with water (30 mL)
  2. dry with materialdried over Na2SO4
  3. customRemoval of the solvent
  4. waitleft an orange oil (378 mg)
  5. customA portion of the oil was purified by preparative HPLC

Sources & evidence

ORD record
ord-fca437c77e05406fb7fc0c40ac893680
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

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