Potassium Carbonate → Ethyl 3-(5-(3-chloro-2-formyl-5-(trifluoromethyl)phenyl)picolinamido)propanoate

HRID 405192Notes

Reaction equation

Br[C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[C:6]([Cl:14])[C:3]=1[CH:4]=[O:5].CC1(C)C(C)(C)OB([C:23]2[CH:24]=[CH:25][C:26]([C:29]([NH:31][CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])=[O:30])=[N:27][CH:28]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:14][C:6]1[C:3]([CH:4]=[O:5])=[C:2]([C:23]2[CH:24]=[CH:25][C:26]([C:29]([NH:31][CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])=[O:30])=[N:27][CH:28]=2)[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=1

Participants

Conditions

Temperature: 90 °C

Procedure

2-Bromo-6-chloro-4-(trifluoromethyl)benzaldehyde (3.4 g, 11.9 mmol) (as described in Example 72, STEP C), ethyl 3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamido)propanoate (5.0 g, 14.3 mmol), Pd(dppf)Cl2 (435 mg, 0.6 mmol), and 2 M K2CO3 (aq) (11.9 mL, 23.8 mmol) were dissolved in 1,4-dioxane (48 mL) and heated to 90° C. After 2 h the temperature was lowered to 80° C. After 14 h the resulting mixture was concentrated, diluted with EtOAc and 4M aqueous NaCl, and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organics were dried (Na2SO4), concentrated, and purified via column chromatography to yield the title compound.

Workup

concentrationAfter 14 h the resulting mixture was concentrated
additiondiluted with EtOAc and 4M aqueous NaCl
customthe layers were separated
extractionThe aqueous layer was extracted with EtOAc
dry with materialthe combined organics were dried (Na2SO4)
concentrationconcentrated
custompurified via column chromatography

Sources & evidence

ORD record: ord-83a59cc59d0f49658fa059799c26fc88
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08748624B2

Reaction notes

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