Piperidine → HCID 89619536, compound

HRID 714601Notes

Reaction equation

HRID 714601 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([C:11]2[CH:16]=[C:15]([O:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[CH:14]=[CH:13][C:12]=2[OH:24])=[O:10])[CH:5]=[CH:6][CH:7]=1.[I:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=O)=[CH:28][CH:27]=1.N1CCCCC1.C1CCN2C(=NCCC2)CC1>C(O)(CC)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:9](=[O:10])[C:11]3[C:12](=[CH:13][CH:14]=[C:15]([O:17][CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][O:19]4)[CH:16]=3)[O:24][CH:30]2[C:29]2[CH:32]=[CH:33][C:26]([I:25])=[CH:27][CH:28]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8082PiperidineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 966574-IodobenzaldehydeHCID 89619898HCID 89619898, compound

Product 1

HCID 89619536HCID 89619536, compoundYield 88.5%

Reagents, catalysts & solvents 1

HCID 6568(+-)-2-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 2-(3-bromophenyl)-1-(2-hydroxy-5-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)ethanone (5.28 g, 13.5 mmol), 4-iodobenzaldehyde (3.29 g, 14.2 mmol), piperidine (0.66 mL, 4.4 mmol), and DBU (0.44 mL, 4.5 mmol) in s-butanol (27 mL) was heated at reflux. Using a Dean-Stark trap, half (13 mL) of the solvent was removed over 40 min, and the reaction was kept at reflux without further concentration for additional 4.5 h. The reaction mixture was cooled to 90° C., i-propanol (27 mL) was added, and the reaction was allowed to cool to room temperature. The large solid pieces were broken down with spatula, and the suspension was stirred overnight (Note #1). The precipitate was collected by filtration to yield 3-(3-bromophenyl)-2-(4-iodophenyl)-6-((tetrahydro-2H-pyran-2-yl)oxy)chroman-4-one (7.23 g, 88%) as a white solid. 1H NMR (DMSO-d6): δ 7.67 (d, 2H), 7.43 (m, 1H), 7.38 (m, 1H), 7.36-7.30 (m, 2H), 7.21 (dd, 2H), 7.18-7.10 (m, 2H), 7.07 (dd, 1H), 5.95 (d, 1H), 5.47 (m, 1H), 4.76 (d, 1H), 3.73 (m, 1H), 3.55 (m, 1H), 1.93-1.68 (m, 3H), 1.68-1.48 (m, 3H).

Workup

  1. temperatureat reflux
  2. customwas removed over 40 min
  3. temperatureat reflux without further concentration for additional 4.5 h
  4. additioni-propanol (27 mL) was added
  5. temperatureto cool to room temperature
  6. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-aa4436802ac24b58b42b0240dfba5b37
Source dataset
uspto-grants-2015_11
Patent number
US09187460B2

Reaction notes

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