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

HRID 1626506Notes

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.C(N(C(C)C)CC)(C)C>ClCCl.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

Conditions

Temperature: 70 °C

Procedure

4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation B; 1.0 g, 2.65 mmol) was diluted with dichloromethane (10 mL) followed by the addition of oxalyl chloride in dichloromethane (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 diisopropyl ethylamine (1.16 ml, 6.64 mmol) were added and the reaction was stirred overnight at ambient temperature, then heated to 70° C. for 4 hours. The reaction mixture was cooled, then loaded directly onto a Biotage 40 cartridge, eluting with 5% ethyl acetate/hexanes to 70% ethyl acetate/hexanes to yield ethyl 7-(4-(6-bromopyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (500 mg, 0.940 mmol, 35.4% yield).

Workup

stirringthe reaction was stirred overnight at ambient temperature
temperatureThe reaction mixture was cooled
washeluting with 5% ethyl acetate/hexanes to 70% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-b5989df01d124a9da848073256a9b0e1
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785445B2

Reaction notes

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