Dimethylformamide → Ethyl 2-(2-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetate

HRID 1964142Notes

Reaction equation

HRID 1964142 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]1[CH2:11][CH2:12][CH2:13][CH:14]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]1=[CH:5]2.CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH:41]([CH3:43])[CH3:42])=[C:36]([C:44]([F:47])([F:46])[F:45])[CH:35]=1>CCOC(C)=O.O>[CH:41]([O:40][C:37]1[CH:38]=[CH:39][C:34]([CH2:33][O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]2[CH2:11][CH2:12][CH2:13][CH:14]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]2=[CH:5]3)=[CH:35][C:36]=1[C:44]([F:45])([F:46])[F:47])([CH3:43])[CH3:42]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 533782354-(Chloromethyl)-1-isopropoxy-2-(trifluoromethyl)benzeneHCID 67249257Ethyl 2-(2-hydroxy-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetate

Product 1

HCID 67248678Ethyl 2-(2-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetateYield 80.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 2-(2-hydroxy-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetate (0.107 g, 0.391 mmol) was dissolved in anhydrous DMF (3.91 mL, 0.391 mmol). Cesium carbonate (0.166 g, 0.509 mmol) was added followed by 4-(chloromethyl)-1-isopropoxy-2-(trifluoromethyl)benzene (0.122 mL, 0.587 mmol) to give a suspension. The reaction was heated at 50° C. for 5 h. The solvent was evaporated in vacuo to give a residue which was dissolved in EtOAc (50 mL) and water (20 mL). The organic layer was washed with water (20 mL), brine (20 mL), and dried over MgSO4. The solvent was evaporated in vacuo to give an oil which was purified by silica gel column chromatography to give the title compound as an oil (0.154 g). LCMS m/z=490.4 [M+H]+; 1H NMR (400 MHz, Acetonitrile-d3) δ ppm 1.24 (t, J=7.14 Hz, 3H), 1.32 (d, J=6.06 Hz, 6H), 1.50-1.64 (m, 1H), 2.1 (m, 3H), 2.55 (dd, J=15.73, 8.02 Hz, 1H), 2.86 (dd, J=15.66, 5.94 Hz, 1H), 3.33-3.47 (m, 1H), 3.79-3.88 (m, 1H), 4.06-4.21 (m, 3H), 4.74 (dt, J=12.09, 6.02 Hz, 1H), 5.04 (s, 2H), 6.13 (s, 1H), 6.81 (dd, J=8.78, 2.46 Hz, 1H), 7.04 (d, J=2.40 Hz, 1H), 7.16 (d, J=8.59 Hz, 1H), 7.19 (d, J=8.84 Hz, 1H), 7.62 (d, J=8.59 Hz, 1H), 7.66 (d, J=1.89 Hz, 1H).

Workup

  1. customto give a suspension
  2. customThe solvent was evaporated in vacuo
  3. customto give a residue which
  4. washThe organic layer was washed with water (20 mL), brine (20 mL)
  5. dry with materialdried over MgSO4
  6. customThe solvent was evaporated in vacuo
  7. customto give an oil which
  8. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a7cb90ed0acc433a9ff8813cfc734311
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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