tert-Butyl acrylate → tert-Butyl (2E)-3-(5-benzyloxy-6-methylpyridin-2-yl)acrylate

HRID 1820954Notes

Reaction equation

[CH3:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=[C:4](I)[N:3]=1.[C:17]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])(=[O:20])[CH:18]=[CH2:19].C(=O)(O)[O-].[Na+]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:9]([O:8][C:7]1[CH:6]=[CH:5][C:4](/[CH:19]=[CH:18]/[C:17]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[N:3][C:2]=1[CH3:1])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 828 mg (2.55 mmol) of 2-methyl-3-benzyloxy-6-iodopyridine (from Step B), 746 μL (5.09 mmol) of tert-butyl acrylate, 535 mg (6.37 mmol) of sodium bicarbonate, 708 mg (255 mmol) of tetrabutylammonium chloride, and 20 mg of crushed 4 A molecular sieve in 10 mL of DMF was added 29 mg (0.13 mmol) of palladium acetate. After stirring at 60° C. for 5 h, the reaction mixture was cooled to rt, diluted with EtOAc (20 mL), and filtered through a cake of Celite. The filtrate was washed with brine (100 mL), H2O (3×100 mL), and brine (100 mL). The organic layer was dried over Na2SO4 and concentrated. Chromatography on a Biotage 40M cartridge using 2:23 v/v EtOAc/hexanes as the eluant afforded 703 mg of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.52 (s, 9H), 2.53 (s, 3H), 5.09 (s, 2H), 6.70 (d, J=15.6, 2H), 7.06 (d, J=8.5, 1H), 7.18 (d, J=8.5, 1H), 7.37-7.42 (m, 5H), 7.52 (d, J=15.8, 2H).

Workup

temperaturethe reaction mixture was cooled to rt
filtrationfiltered through a cake of Celite
washThe filtrate was washed with brine (100 mL), H2O (3×100 mL), and brine (100 mL)
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-829c6f7c06b74fecaf94a05e25b9224b
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07605171B2

Reaction notes

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