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

HRID 1626415Notes

Reaction equation

HRID 1626415 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.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[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

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 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-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (1 g, 2.65 mmol) was diluted with DCM (10 mL) followed by the addition of oxalyl chloride in DCM (2M) (1.46 mL, 2.92 mmol) and DMF (1 drop). After stirring for 20 minutes, 6-bromopyridin-2-amine (0.505 g, 2.92 mmol) and DIEA (1.16 mL, 6.64 mmol) were added and the reaction was stirred overnight at ambient temperature. The reaction was loaded directly onto a biotage 40 cartridge and eluted with 5% ethyl acetate/hexanes to 70% ethyl acetate/hexanes to provide the desired product.

Workup

  1. stirringthe reaction was stirred overnight at ambient temperature
  2. washeluted with 5% ethyl acetate/hexanes to 70% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f27019db60dc4b83813d1d1256e87504
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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