1-Iodopropane → 5,5-Dimethyl-3-propyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid

HRID 1665930Notes

Reaction equation

HRID 1665930 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)[CH2:16][CH3:17]>C1COCC1>[CH3:1][C:2]1([CH3:14])[CH2:13][CH2:12][C:5]2=[C:6]([C:9]([OH:11])=[O:10])[S:7][C:8]([CH2:15][CH2:16][CH3:17])=[C:4]2[CH2:3]1

Participants

4

Reactant 2

HCID 336431-IodopropaneHCID 57508882HCID 57508882, compound

Product 1

HCID 574374195,5-Dimethyl-3-propyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acidYield 8.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (−75° C.) solution of 5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (2.0 g, 9.51 mmol) in THF (40 mL) tert.-butyllithium (15 mL, 1.5 N in pentane) is slowly added. The mixture is stirred at −78° C. for 15 min before n-propyliodide (5.22 g, 30.7 mmol) is added. Stirring is continued at −78° C. for 45 min before the reaction is quenched by adding water/methanol 1:1 (10 mL). The mixture is allowed to warm to rt, diluted with tert.-butyl methylether and 10% aq. citric acid solution. The mixture is extracted twice with EA, the combined organic extracts are washed with brine, dried over Na2SO4 and concentrated. The crude product is purified by prep. HPLC to give 5,5-dimethyl-3-propyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (200 mg) as a colourless resin; LC-MS: tR=1.04 min, [M+1]=253.31; 1H NMR (CDCl3): δ 2.98 (t, J=7.0 Hz, 2H), 2.63 (t, J=7.6 Hz, 2H), 2.36 (s br, 1H), 2.26 (s, 2H), 1.63 (hex, J=7.6 Hz, 2H), 1.51 (t, J=7.0 Hz, 2H), 0.95 (t, J=7.6 Hz, 3H), 0.94 (s, 6H).

Workup

  1. additionis slowly added
  2. additionis added
  3. customis quenched
  4. additionby adding water/methanol 1:1 (10 mL)
  5. additiondiluted with tert.-butyl methylether and 10% aq. citric acid solution
  6. extractionThe mixture is extracted twice with EA
  7. washthe combined organic extracts are washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-543c2e131eb241ef8a71ff26b89b1bd9
Source dataset
uspto-grants-2011_10
Patent number
US08039644B2

Reaction notes

Loading…