Pyridine → HCID 67287963, compound

HRID 1626434Notes

Reaction equation

HRID 1626434 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23].C(Cl)(=O)C(Cl)=O.N1C=CC=CC=1.Cl.[C:40]1([CH3:53])[CH:45]=[CH:44][C:43]([C:46]2[N:51]=[C:50]([NH2:52])[CH:49]=[CH:48][CH:47]=2)=[CH:42][CH:41]=1>ClCCCl.CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](=[O:18])[NH:52][C:50]3[CH:49]=[CH:48][CH:47]=[C:46]([C:43]4[CH:42]=[CH:41][C:40]([CH3:53])=[CH:45][CH:44]=4)[N:51]=3)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acidHCID 67287111HCID 67287111, compound

Product 1

HCID 67287963HCID 67287963, compoundYield 60.72%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation B; 56 mg, 0.1486 mmol) in 1,2-dichloroethane (0.15 ml) and DMF (1 drop) was added oxalyl chloride (15.56 μl, 0.1783 mmol), and the reaction was stirred for 2 hours. To this, pyridine (0.6 ml) and 6-p-tolylpyridin-2-amine hydrochloride (36.08 mg, 0.1635 mmol) were added, and the reaction was heated to 80° C. for 16 hours. The reaction was diluted with EtOAc and washed with 10% citric acid, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by silica gel chromatography, eluting with a gradient of 5-70% EtOAc/hexanes to yield the desired compound (49 mg, 0.09024 mmol, 60.72% yield).

Workup

  1. washwashed with 10% citric acid, saturated sodium bicarbonate, and saturated sodium chloride
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by silica gel chromatography
  6. washeluting with a gradient of 5-70% EtOAc/hexanes

Sources & evidence

ORD record
ord-bce07c5dd1e54a18abcd7993f0a27a7a
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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