HCID 22025646, compound → HCID 22025620, compound

HRID 1793002Notes

Reaction equation

HRID 1793002 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]=[CH2:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11]1[C:23]([F:24])=[C:22]([F:25])[CH:21]=[CH:20][C:12]=1[C:13]([NH:15][O:16][CH2:17][CH2:18][OH:19])=[O:14]>O1CCCC1.[Pd].CO>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH3:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11]1[C:23]([F:24])=[C:22]([F:25])[CH:21]=[CH:20][C:12]=1[C:13]([NH:15][O:16][CH2:17][CH2:18][OH:19])=[O:14]

Participants

5

Reactant 1

HCID 22025646HCID 22025646, compound2×

Product 1

HCID 22025620HCID 22025620, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of the product of Example 2, Step D, 2-(2-chloro-4-vinyl-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (0.291 g, 0.789 mmol) in tetrahydrofuran (16 mL) was hydrogenated over 10% palladium on carbon (0.08 g) at 6900 psig at room temperature for 17 hours. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to afford a crystalline solid. The solid was dissolved in methanol and concentrated to near dryness. Ether (10 mL) was added and the mixture was allowed to stand at ambient temperature for 6 hours. during which crystallization ensued. The white crystals were filtered, washed with a small volume of ether, and dried in vacuo at 60° C. overnight yielding 2-(2-chloro-4-ethyl-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (222 mg): m.p. 142.5–145° C.; 1H NMR (400 MHz, DMSO-d6) δ 11.94 (br s, 1 H), 8.85 (br s, 1 H), 7.44 (br t, J=6.4 Hz, 1 H), 7.30 (d, J=2.0 Hz, 1 H), 7.22–7.15 (m, 1 H), 7.05 (dd, J=8.3, 2.0 Hz, 1 H), 6.75 (dd, J=8.3, 6.3 Hz, 1 H), 4.71 (br s, 1 H), 3.89 (br s, 2 H), 3.59 (br s, 2 H), 2.54 (q, J=7.6 Hz, 2 H), 1.15 (t, J=7.6 Hz, 3 H); 19F NMR (376 MHz, DMSO-d6) δ −132.7, −142.0; MS (APCI+)=371.0. Anal. Calcd/found for C17H17ClF2N2O3: C, 55.07/55.14; H, 4.62/4.51; N, 7.56/7.38; F, 10.25/9.98.

Workup

  1. customThe catalyst was removed by filtration
  2. concentrationthe filtrate was concentrated in vacuo
  3. customto afford a crystalline solid
  4. concentrationconcentrated
  5. additionEther (10 mL) was added
  6. customduring which crystallization
  7. filtrationThe white crystals were filtered
  8. washwashed with a small volume of ether
  9. customdried in vacuo at 60° C. overnight

Sources & evidence

ORD record
ord-73439d27f39b4390aed46e812a67376f
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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