Methyl iodide → 3-Ethyl-4-isobutylthiophene-2-carboxylic acid

HRID 1676108Notes

Reaction equation

[CH2:1]([C:5]1[C:6]([CH3:13])=[C:7]([C:10]([OH:12])=[O:11])[S:8][CH:9]=1)[CH:2]([CH3:4])[CH3:3].[Li][CH2:15]CCC.IC>C1COCC1>[CH2:13]([C:6]1[C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])=[CH:9][S:8][C:7]=1[C:10]([OH:12])=[O:11])[CH3:15]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 4-isobutyl-3-methyl-thiophene-2-carboxylic acid (991 mg, 5.0 mmol) in THF (30 mL), tert.-BuLi (7.3 mL, 11 mmol, 1.5 M in pentane) is slowly added at −78° C. The mixture is stirred at −78° C. for 1 h, then iodomethane (1.6 mL, 25.7 mmol) is added. The mixture is stirred and is allowed to warm to rt over a period of 15 h before the reaction is quenched with 1 N aq. HCl (50 mL) and extracted with DCM (1×100 mL, 2×50 mL). The combined organic extracts are dried (MgSO4), filtered and evaporated. The residue is purified by CC on silica gel eluting with a gradient of EA in hexane to give 3-ethyl-4-isobutyl-thiophene-2-carboxylic acid (325 mg) as a yellow solid; LC-MS: tR=0.98 min, 1H NMR (CD3OD): δ 7.22 (s, 1H), 2.94 (q, J=7.6 Hz, 2H), 2.42 (d, J=7.0 Hz, 2H), 1.86 (hept, J=7.0 Hz, 1H), 1.11 (t, J=7.6 Hz, 3H), 0.93 (d, J=7.0 Hz, 6H).

Workup

stirringThe mixture is stirred
temperatureto warm to rt over a period of 15 h before the reaction
customis quenched with 1 N aq. HCl (50 mL)
extractionextracted with DCM (1×100 mL, 2×50 mL)
dry with materialThe combined organic extracts are dried (MgSO4)
filtrationfiltered
customevaporated
customThe residue is purified by CC on silica gel eluting with a gradient of EA in hexane

Sources & evidence

ORD record: ord-a688edf198e44ebbb05d1c263a353ca9
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003800B2

Reaction notes

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