2-Bromo-isonicotinic acid methyl ester → Methyl 2-(4-methylthiazol-2-yl)isonicotinate

HRID 594291Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH3:12][C:13]1[N:14]=[C:15]([Sn](CCCC)(CCCC)CCCC)[S:16][CH:17]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:12][C:13]1[N:14]=[C:15]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])[S:16][CH:17]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of commercially available methyl 2-bromoisonicotinate (2.750 g; 12.70 mmol), 4-methyl-2-(tributylstannyl)thiazole (4.942 g; 12.70 mmol), copper iodide CuI (242 mg; 1.27 mmol), and Pd(PPh3)4 (1.471 g; 1.27 mmol) in anh. DMF (55 ml) was heated to 90° C., under nitrogen, for 18 h. After cooling to rt, the reaction mixture was filtered over a pad of celite, and the separated solids were washed with AcOEt. The organic layer was washed with water and brine, dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (heptane/AcOEt=7/3) afforded methyl 2-(4-methylthiazol-2-yl)isonicotinate as a yellow solid. LC-MS (conditions A): tR=0.74 min.; [M+H]+: 234.94 g/mol.

Workup

temperatureAfter cooling to rt
filtrationthe reaction mixture was filtered over a pad of celite
washthe separated solids were washed with AcOEt
washThe organic layer was washed with water and brine
dry with materialdried over anh. MgSO4
filtrationfiltered
concentrationconcentrated to dryness under reduced pressure
customPurification by FC (heptane/AcOEt=7/3)

Sources & evidence

ORD record: ord-1a99e02aeba446ea9e2a5ea23c16c7cd
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242970B2

Reaction notes

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