1,1'-Carbonyldiimidazole → HCID 10126224, compound

HRID 1835651Notes

Reaction equation

HRID 1835651 reaction equation
[NH2:1][O:2][CH2:3][CH2:4][OH:5].[F:6][C:7]1[C:8]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:19]=2)=[C:9]([CH:13]=[CH:14][C:15]=1[F:16])[C:10](O)=[O:11].C1N=CN(C(N2C=NC=C2)=O)C=1>C1COCC1>[F:6][C:7]1[C:15]([F:16])=[CH:14][CH:13]=[C:9]([C:10]([NH:1][O:2][CH2:3][CH2:4][OH:5])=[O:11])[C:8]=1[NH:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 3014186Ethanol, 2-(aminooxy)-2×HCID 12135107HCID 12135107, compound

Product 1

HCID 10126224HCID 10126224, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

This material was then coupled directly with 2-(aminooxy)ethanol as follows: The crude 3,4-difluoro-2-[[4-(methoxycarbonyl)-phenyl]amino]benzoic acid was dissolved in dry THF (20 mL) to which was added CDI (1.63 g, 10.0 mmol). This reaction mixture was stirred at room temperature for 2 hours, then a solution of 2-(aminooxy)ethanol (1.55 g, 20.1 mmol) in dry THF (10 mL) was added and the reaction allowed to stir at room temperature overnight. The reaction solvent was removed under reduced pressure and the resulting oil dissolved in EtOAc (200 mL) which was washed sequentially with 1 M HCl (100 mL), water (100 mL), and brine (100 mL). The solution was dried (Na2SO4), the solvent removed under reduced pressure and the crude oil purified by chromatography on flash silica (10% EtOAc as eluant) to give methyl 4-[[2,3-difluoro-6-[[(2-hydroxyethoxy)amino]carbonyl]phenyl]amino]benzoate (0.889 g, 48%) as a white solid; mp (EtOAc/hexanes) 158-160° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.64 (br s, 1 H), 8.76 (br s, 1 H), 7.78 (d, J=8.8 Hz, 2 H), 7.41-7.27 (m, 2 H), 6.80 (dd, J=8.8, 1.8 Hz, 2 H), 4.67 (br s, 1 H), 3.78 (s, 3 H), 3.76 (t, J=4.8 Hz, 2 H), 3.50 (t, J=4.6 Hz, 2 H). Anal Calcd for C17H16F2N2O5: C, 55.7; H, 4.4; N, 7.7. Found C, 55.7; H, 4.4; N, 7.6.

Workup

  1. stirringto stir at room temperature overnight
  2. customThe reaction solvent was removed under reduced pressure
  3. dissolutionthe resulting oil dissolved in EtOAc (200 mL) which
  4. washwas washed sequentially with 1 M HCl (100 mL), water (100 mL), and brine (100 mL)
  5. dry with materialThe solution was dried (Na2SO4)
  6. customthe solvent removed under reduced pressure
  7. customthe crude oil purified by chromatography on flash silica (10% EtOAc as eluant)

Sources & evidence

ORD record
ord-5386ef69fbc84d51b3c068e4c33eae50
Source dataset
uspto-grants-2004_08
Patent number
US06770778B2

Reaction notes

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