Sodium Bicarbonate → ethyl 5-methoxy-4-methyl-1H-indole-2-carboxylate

HRID 1964147Notes

Reaction equation

Br[C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[NH:6]2.[Cl-].C[Zn+].[C:21]([O-])(O)=O.[Na+]>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:12][O:11][C:10]1[C:2]([CH3:21])=[C:3]2[C:7](=[CH:8][CH:9]=1)[NH:6][C:5]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4]2

Participants

Conditions

Temperature: 65 °C

Procedure

To a reaction mixture of ethyl 4-bromo-5-methoxy-1H-indole-2-carboxylate (1 g, 3.35 mmol) and bis(tri-t-butylphosphine)palladium (0) (0.171 g, 0.335 mmol) in THF (10 mL) was added a 2 M solution of methylzinc(II) chloride in THF (5.03 mL, 10.06 mmol) at room temperature. The reaction was stirred at 65° C. for 2 h, cooled down, and added saturated aqueous NaHCO3 solution. The solid was filtered off through celite and washed with ethyl acetate. The filtrate was extracted with ethyl acetate. The combined organics were dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column chromatography to give the title compound as white solid (712 mg). LCMS m/z=234.2 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.42 (t, J=7.1 Hz, 3H), 2.44 (s, 3H), 3.87 (s, 3H), 4.41 (q, J=7.1 Hz, 2H), 7.05 (d, J=9.0 Hz, 1H), 7.19-7.24 (m, 2H), 8.81 (s, 1H).

Workup

temperaturecooled down
filtrationThe solid was filtered off through celite
washwashed with ethyl acetate
extractionThe filtrate was extracted with ethyl acetate
dry with materialThe combined organics were dried over anhydrous Na2SO4
concentrationconcentrated
customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-84888d7bdf904eb2bf351d33cb69efa1
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415484B2

Reaction notes

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