Citric Acid → 3-Ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid

HRID 2240791Notes

Reaction equation

[CH3:1][C:2]1([CH3:14])[CH2:13][CH2:12][C:5]2=[C:6]([C:9]([OH:11])=[O:10])[S:7][CH:8]=[C:4]2[CH2:3]1.[CH2:15](I)[CH3:16].O.CO.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.C([Li])(C)(C)C>[CH2:15]([C:8]1[S:7][C:6]([C:9]([OH:11])=[O:10])=[C:5]2[CH2:12][CH2:13][C:2]([CH3:14])([CH3:1])[CH2:3][C:4]=12)[CH3:16]

Participants

Conditions

Temperature: -78 °C

Procedure

To a cooled solution (−78° C.) of 5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (960 mg, 4.57 mmol) in THF (19 mL), tert.-butyllithium (8 mL, 1.5 M solution in pentane) is added. The mixture is stirred at −78° C. for 10 min before ethyliodide (3.80 g, 24.37 mmol) is added. The reaction mixture is stirred at −78° C. for 3 h. Water/methanol 1:1 (8 mL) followed by 10% aq. citric acid solution is added and the mixture is extracted with EA. The combined organic extracts are washed with brine, dried over Na2SO4 and evaporated. The remaining solid is suspended in acetonitrile (6 mL), heated to 60° C., cooled to rt, filtered and dried to give 3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (640 mg) as a slightly beige solid; LC-MS: tR=1.01 min, [M+1+CH3CN]=280.10.

Workup

additionis added
additionis added
extractionthe mixture is extracted with EA
washThe combined organic extracts are washed with brine
dry with materialdried over Na2SO4
customevaporated
temperatureheated to 60° C.
temperaturecooled to rt
filtrationfiltered
customdried

Sources & evidence

ORD record: ord-a828137dbf65476cabd2276ce6266b32
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723378B2

Reaction notes

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