Oxalyl chloride → HCID 67080868, compound

HRID 1048196Notes

Reaction equation

HRID 1048196 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.[CH3:33][O:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][C:36]=1[CH2:45][CH2:46][NH2:47].CCN(C(C)C)C(C)C>ClCCl.CN(C=O)C>[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:47][CH2:46][CH2:45][C:36]3[CH:37]=[CH:38][C:39]([C:41]([F:43])([F:44])[F:42])=[CH:40][C:35]=3[O:34][CH3:33])=[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

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acidHCID 58244424HCID 58244424, compound

Product 1

HCID 67080868HCID 67080868, compoundYield 58.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A portion of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1; 0.7 g, 1.86 mmol) was diluted with dichloromethane (1 mL) followed by the addition of oxalyl chloride in dichloromethane (1.02 ml, 2.04 mmol) and DMF (1 drop). After stirring for 10 minutes, 2-(2-methoxy-4-(trifluoromethyl)phenyl)ethanamine (Preparation 9; 0.448 g, 2.04 mmol) and DIEA (1.13 ml, 6.50 mmol) were added, and the reaction was stirred for 2 hours. The reaction was loaded directly onto a biotage 25 cartridge and eluted with 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes to yield ethyl 6-chloro-7-(4-(2-methoxy-4-(trifluoromethyl)phenethylcarbamoyl)phenoxy)chroman-4-carboxylate (624 mg, 1.08 mmol, 58.1% yield).

Workup

  1. stirringthe reaction was stirred for 2 hours
  2. washeluted with 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-69b056df05b145f6b92d8ffd982faf7d
Source dataset
uspto-grants-2013_10
Patent number
US08569522B2

Reaction notes

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