Isopropyl iodide → 3-Isopropyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid

HRID 1665931Notes

Reaction equation

HRID 1665931 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.[CH:15](I)([CH3:17])[CH3:16]>C1COCC1.C([Li])(C)(C)C.O>[CH: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)([CH3:17])[CH3:16]

Participants

6

Reactant 2

HCID 6362Isopropyl iodideHCID 57508882HCID 57508882, compound

Product 1

HCID 575088863-Isopropyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acidYield 20.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 178418306HCID 178418306, compoundSolvent

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 (2.00 g, 9.51 mmol) in THF (35 mL), tert.-butyllithium (16 mL, 1.5 M solution in pentane) is added. The mixture is stirred at −78° C. for 10 min before isopropyliodide (7.60 g, 48.7 mmol) is added. The reaction mixture is stirred at −78° C. for 3 h, then at rt for 3 d. The reaction mixture is diluted with water and extracted twice with EA. The combined organic extracts are dried over Na2SO4 and evaporated. The crude product is purified by CC on silica gel eluting with DCM/TBME 20:1 followed by prep. HPLC to give 3-isopropyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (500 mg) as a white solid; LC-MS: tR=1.04 min, [M+1+CH3CN]=294.16.

Workup

  1. additionis added
  2. waitat rt for 3 d
  3. extractionextracted twice with EA
  4. dry with materialThe combined organic extracts are dried over Na2SO4
  5. customevaporated
  6. customThe crude product is purified by CC on silica gel eluting with DCM/TBME 20:1

Sources & evidence

ORD record
ord-d27c1677ab3e4611a5851ece5e15c755
Source dataset
uspto-grants-2011_10
Patent number
US08039644B2

Reaction notes

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