Oxalyl chloride → HCID 86664398, compound

HRID 1626510Notes

Reaction equation

HRID 1626510 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.[F:33][C:34]([F:46])([F:45])[C:35]1[CH:44]=[CH:43][C:38]2[N:39]=[C:40]([NH2:42])[S:41][C:37]=2[CH:36]=1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C=O.CO>[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:19])[NH:42][C:40]3[S:41][C:37]4[CH:36]=[C:35]([C:34]([F:46])([F:33])[F:45])[CH:44]=[CH:43][C:38]=4[N:39]=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 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 27359552-Amino-6-(trifluoromethyl)benzothiazoleHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid

Product 1

HCID 86664398HCID 86664398, compoundYield 32.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation B; 100 mg, 0.265 mmol) was diluted with dichloromethane (5 mL) followed by the addition of oxalyl chloride in dichloromethane (2M) (146 μL, 0.292 mmol) and dimethylformamide (1 drop). After stirring for 30 minutes a small aliquot was diluted with methanol for 5 minutes. Thin layer chromatography of this aliquot showed complete conversion to methyl ester. 6-(Trifluoromethyl)benzo[d]thiazol-2-amine (63.7 mg, 0.292 mmol) and diisopropyl ethylamine (116 μL, 0.664 mmol) were added and the reaction was stirred at 35° C. for 1 hour. The reaction was loaded directly onto a Biotage 25 cartridge and eluted with 5% ethyl acetate/hexanes to 70% ethyl acetate/hexanes to yield ethyl 6-chloro-7-(4-(6-(trifluoromethyl)benzo[d]thiazol-2-ylcarbamoyl)phenoxy)chroman-4-carboxylate (50 mg, 0.0867 mmol, 32.7% yield).

Workup

  1. stirringthe reaction was stirred at 35° C. for 1 hour
  2. washeluted with 5% ethyl acetate/hexanes to 70% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-a75130be1f944265ad52ff250b8bcad4
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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