Tosylmethyl isocyanide → Ethyl 4-phenyl-1H-pyrrole-3-carboxylate

HRID 1295750Notes

Reaction equation

C[Si](C)(C)[N-][Si](C)(C)C.[Li+].S([CH2:21][N+:22]#[C-:23])(C1C=CC(C)=CC=1)(=O)=O.[C:24]([O:34][CH2:35][CH3:36])(=[O:33])/[CH:25]=[CH:26]/[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1.C(OCC)(=O)C>[C:24]([C:25]1[C:26]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[CH:23][NH:22][CH:21]=1)([O:34][CH2:35][CH3:36])=[O:33]

Participants

Conditions

Temperature: 25 °C

Procedure

To a 1.0 M solution of lithium hexamethyldisilazide in THF (41 mL, 41 mmol) at −78° C. was added dropwise over 45 min. a solution of tosylmethyl isocyanide (8.1 g, 41 mmol) in THF. After the reaction was stirred for an additional 45 min. a solution of trans-ethyl cinnamate (7.3 g, 41 mmol) in THF (40 mL) was added over 40 min. The reaction was warmed to 25° C. and stirred for 5 h. The reaction was diluted with ethyl acetate and washed with sat. aqueous NaHCO3. The aqueous layer was extracted three times with ethyl acetate, dried (Na2SO4), concentrated and purified by chromatography on silica gel eluting with a gradient of 20-30% ethyl acetate in hexanes to provide 3.4 g (41%) of 3-carboethoxy-4-phenylpyrrole as an off-white solid. 1H NMR (CDCl3): δ 8.62 (br s, 1H), 7.57-7.12 (m, 6H), 6.73 (s, 1H), 4.19 (q, J=7.1 Hz, 2H), 1.23 (t, J=7.1 Hz, 3H)

Workup

additionwas added over 40 min
washwashed with sat. aqueous NaHCO3
extractionThe aqueous layer was extracted three times with ethyl acetate
dry with materialdried (Na2SO4)
concentrationconcentrated
custompurified by chromatography on silica gel eluting with a gradient of 20-30% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-c508d0a379f34397a1b0557ed0d21c38
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07244733B2

Reaction notes

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