Dimethylformamide → HCID 58674485, compound

HRID 1994132Notes

Reaction equation

HRID 1994132 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.Cl[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([C:20]([NH:22][CH3:23])=[O:21])[CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C[N:31]([CH:33]=O)C>>[NH:31]([C:10](=[O:12])[CH2:9][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([O:1][C:14]2[CH:19]=[CH:18][N:17]=[C:16]([C:20]([NH:22][CH3:23])=[O:21])[CH:15]=2)=[CH:7][CH:6]=1)[C:33]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 103943-(4-Hydroxyphenyl)propionic acidHCID 10796Cesium carbonateHCID 14768144-Chloro-N-methylpicolinamide

Product 1

HCID 58674485HCID 58674485, compoundYield 37%

Conditions

Temperature
100 °C

Procedure

A mixture of 3-(4-hydroxyphenyl)propanoic acid (10.7 g, 64.5 mmol), 4-chloro-N-methylpicolinamide (10.0 g, 58.6 mmol) and cesium carbonate (57.3 g, 175.8 mmol) was stirred in DMF and heated at 100° C. overnight. After cooling to rt, the mixture was filtered and washed with EtOAc to remove cesium carbonate. The remaining solid was dissolved in a minimal amount of water and the pH of the solution was adjusted to 4 by the dropwise addition of a sat. oxalic acid solution. The solution was extracted with DCM, the organic solutions washed with water and brine, dried over MgSO4, filtered, and concentrated. The resulting solid was recrystallized from EtOAc to give the desired product as a pale cream solid (5.07 g, 37%). 1H NMR (400 MHz, d6-DMSO) δ: 12.13 (s, 1H), 8.70-8.78 (m, 1H), 8.49 (d, J=5.6 Hz, 1H), 7.34-7.39 (m, 3H), 7.11-7.14 (m, 3H), 2.87 (br t, J=7.6 Hz, 2H), 2.77 (d, J=4.8 Hz, 3H), and 2.57 (br t, J=7.6 Hz, 2H).

Workup

  1. temperatureAfter cooling to rt
  2. filtrationthe mixture was filtered
  3. washwashed with EtOAc
  4. customto remove cesium carbonate
  5. dissolutionThe remaining solid was dissolved in a minimal amount of water
  6. additionthe pH of the solution was adjusted to 4 by the dropwise addition of a sat. oxalic acid solution
  7. extractionThe solution was extracted with DCM
  8. washthe organic solutions washed with water and brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe resulting solid was recrystallized from EtOAc

Sources & evidence

ORD record
ord-95a742f2ce1b4cb2a24b801c3886316a
Source dataset
uspto-grants-2010_01
Patent number
US07652041B2

Reaction notes

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