Oxalyl chloride → HCID 67080492, compound

HRID 510619Notes

Reaction equation

HRID 510619 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.[Cl:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][CH2:41][NH2:42])=[CH:36][CH:35]=1.C(N(C(C)C)CC)(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:14]=[CH:15][C:16]([C:17](=[O:19])[NH:42][CH2:41][CH2:40][C:37]3[CH:38]=[CH:39][C:34]([Cl:33])=[CH:35][CH:36]=3)=[CH:20][CH:21]=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 674302-(4-Chlorophenyl)ethylamineHCID 81531DiisopropylethylamineHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid

Product 1

HCID 67080492HCID 67080492, compoundYield 105.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1) (100 g, 265.40 mmol) was dissolved in dry dichloromethane (750 ml) and few drops of DMF. Oxalyl Chloride (24.310 ml, 278.67 mmol) was slowly added to the mixture under nitrogen stream over a period of 0.5 hours at ambient temperature. Gas evolution was observed. The mixture was stirred for 5 hours at ambient temperature and cooled in an ice bath. 2-(4-Chlorophenyl)ethanamine (40.602 ml, 291.94 mmol) and diisopropylethylamine (55.624 ml, 318.48 mmol) were added. The mixture was warmed to ambient temperature and stirred for 16 hours. The crude mixture was transferred to a separatory funnel and washed with 1N HCl, water, and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting crude solid was further dried under high vacuum to provide 143.5 g of a pink solid. This solid was recrystallized from hot EtOAc/hexanes to provide 130.0 g of the title compound as a light purple solid.

Workup

  1. temperaturecooled in an ice bath
  2. temperatureThe mixture was warmed to ambient temperature
  3. stirringstirred for 16 hours
  4. washwashed with 1N HCl, water, and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting crude solid was further dried under high vacuum

Sources & evidence

ORD record
ord-428e998ae87840b8a30d7ed4c62049cc
Source dataset
uspto-grants-2015_08
Patent number
US09096567B2

Reaction notes

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