Oxalyl chloride → Ethyl 7-(4-(6-bromopyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate

HRID 1626428Notes

Reaction equation

HRID 1626428 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]([OH:19])=O)=[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.[Br:33][C:34]1[N:39]=[C:38]([NH2:40])[CH:37]=[CH:36][CH:35]=1>ClC(Cl)C.CN(C=O)C.N1C=CC=CC=1.CCOC(C)=O>[Br:33][C:34]1[N:39]=[C:38]([NH:40][C:17]([C:16]2[CH:15]=[CH:14][C:13]([O:12][C:11]3[CH:10]=[C:9]4[C:4]([CH:5]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:6][CH2:7][O:8]4)=[CH:3][C:2]=3[Cl:1])=[CH:21][CH:20]=2)=[O:19])[CH:37]=[CH:36][CH:35]=1

Participants

8

Reactant 3

HCID 65578Oxalyl chlorideHCID 3008092-Amino-6-bromopyridineHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid

Product 1

HCID 86664393Ethyl 7-(4-(6-bromopyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylateYield 85.02%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolventHCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation B; 1.00 g, 2.654 mmol) in dichloroethane (2.6 ml) and DMF (1 drop) was added oxalyl chloride (0.2778 ml, 3.185 mmol), and the reaction was stirred at ambient temperature for 2 hours. The reaction was diluted with pyridine (10 ml), and 6-bromopyridin-2-amine (0.9183 g, 5.308 mmol) was added. The reaction was heated to 80° C. for 16 hours, then cooled to ambient temperature and diluted with EtOAc. The reaction was washed with 1M hydrochloric 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 on silica gel eluting with a linear gradient of 5-70% EtOAc/hexanes to yield the desired compound (1.2 g, 2.257 mmol, 85.02% yield).

Workup

  1. additionwas added
  2. temperatureThe reaction was heated to 80° C. for 16 hours
  3. temperaturecooled to ambient temperature
  4. washThe reaction was washed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified on silica gel eluting with a linear gradient of 5-70% EtOAc/hexanes

Sources & evidence

ORD record
ord-fc3978ce981e46628f2d15d3433a283d
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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