Cyclohexane → 4-Oxo-4,5,6,7-tetrahydro-benzo[b]thiophene-2-carboxylic acid tert-butyl ester

HRID 908336Notes

Reaction equation

HRID 908336 reaction equation
[O:1]=[C:2]1[C:10]2[CH:9]=[C:8]([C:11]([OH:13])=[O:12])[S:7][C:6]=2[CH2:5][CH2:4][CH2:3]1.C1CCCCC1.ClC(Cl)(Cl)C(=N)O[C:24]([CH3:27])([CH3:26])[CH3:25]>B(F)(F)F.CCOCC.ClCCl>[C:24]([O:12][C:11]([C:8]1[S:7][C:6]2[CH2:5][CH2:4][CH2:3][C:2](=[O:1])[C:10]=2[CH:9]=1)=[O:13])([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 3

HCID 8078CyclohexaneHCID 2734700Tert-butyl 2,2,2-trichloroethanimidate3×HCID 147215634-Oxo-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxylic acid

Product 1

HCID 592628594-Oxo-4,5,6,7-tetrahydro-benzo[b]thiophene-2-carboxylic acid tert-butyl esterYield 89.1%

Reagents, catalysts & solvents 2

HCID 8000Boron trifluoride etherateCatalystHCID 6344DichloromethaneSolvent

Procedure

4-Oxo-4,5,6,7-tetrahydro-benzo[b]thiophene-2-carboxylic acid (Behringer, H.; Falkenberg, K. Chem. Ber., 1966, 99, 3309) (7.69 g, 39.19 mmol) was suspended in 120 mL 2:1 cyclohexane: dichloromethane. Tert-butyl 2,2,2-trichloroacetimidate (17.13 g, 78.38 mmol) was added in one portion, followed by boron trifluoride diethyl etherate (87.8 mg, 6.19 μmol, 0.16 mol %). The resultant slurry was stirred vigorously for 1.5 hours and a further portion of tert-butyl 2,2,2-trichloroacetimidate (8.57 g, 39.19 mmol) was added. Stirring was continued overnight. Further portions of tert-butyl 2,2,2-trichloroacetimidate (8.57 g, 39.19 mmol) were added at 1.5 hours and 3 hours and after a further 3 hours the reaction was quenched by cautious addition of solid NaHCO3 (˜1 g). Silica was added (˜80 mL) and the resulting suspension was concentrated under reduced pressure. The resulting crude mixture was purified by silica gel chromatography (20% EtOAc in hexanes on 1 L of silica) to afford the title compound as a light yellow solid (8.81 g, 89% yield). MS (ES+) 253. δH (CDCl3) 1.5-1.6 (9H, s), 2.2-2.3 (2H, m), 2.5-2.6 (2H, m), 3.0-3.1 (2H, m), 7.9 (1H, s).

Workup

  1. stirringStirring
  2. waitwas continued overnight
  3. customwas quenched by cautious addition of solid NaHCO3 (˜1 g)
  4. additionSilica was added (˜80 mL)
  5. concentrationthe resulting suspension was concentrated under reduced pressure
  6. customThe resulting crude mixture was purified by silica gel chromatography (20% EtOAc in hexanes on 1 L of silica)

Sources & evidence

ORD record
ord-14d4daefff6c44529af597962ae87199
Source dataset
uspto-grants-2011_09
Patent number
US08017619B2

Reaction notes

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