tert-Butyl acetate → Tert-butyl 2-(6-methylpyridin-2-yl)acetate

HRID 1910059Notes

Reaction equation

[C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])(=[O:3])[CH3:2].Cl[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[N:11]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl-].[NH4+]>C1(C)C=CC=CC=1.O>[CH3:16][C:12]1[N:11]=[C:10]([CH2:2][C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:3])[CH:15]=[CH:14][CH:13]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of tert-butyl acetate (1.013 mL, 7.50 mmol), 2-chloro-6-methylpyridine (638 mg, 5 mmol), chloro(2-di-t-butylphosphino-2′,4′,6′-tri-1-propyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) (34.3 mg, 0.050 mmol) in Toluene (10 mL) at 0° C. in a 100-mL round bottom flask under N2 was added a solution of LHMDS (1M in toluene) (15.00 mL, 15.00 mmol) pre-cooled to 0° C. The reaction was stirred for 30 minutes. LCMS indicated the reaction was complete, so it was poured into ammonium chloride (aqueous, saturated) and water (1:1, 40 mL), and extracted with ethyl acetate (3×100 mL). The combined organics were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography (0-25% EtOAc in hexanes) to afford 1,1-dimethylethyl (6-methyl-2-pyridinyl)acetate (918 mg, 4.43 mmol, 89% yield) as a yellow oil. LC-MS (ES) m/z=208 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.41 (s, 9H), 2.44 (s, 3H), 3.68 (s, 1H), 7.12 (t, J=7.33 Hz, 2H), 7.64 (t, J=7.71 Hz, 1H).

Workup

extractionextracted with ethyl acetate (3×100 mL)
dry with materialThe combined organics were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography (0-25% EtOAc in hexanes)

Sources & evidence

ORD record: ord-07ba28339efe415b896ec6d54a74717f
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598156B2

Reaction notes

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