Reaction #163439

Reaction equation

solution

N-[(5Z)-2-tert-butyl-4-formylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide

(bromomethyl)cyclobutane

magnesium

iodine

→

title compound

Yield 53.2%

N-[(5Z)-2-tert-butyl-4-(2-cyclobutyl-1-hydroxyethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide

Yield 53.2%

Solvents

THF

THF

Conditions

Workup

1. 1
   Temperaturecooled to −40° C.
2. 2
   Temperatureto warm to room temperature
3. 3
   Otherquenched with saturated aqueous NH4Cl
4. 4
   Extractionextracted with EtOAc (2×)
5. 5
   Dryingdried (MgSO4)
6. 6
   Filtrationfiltered
7. 7
   Othersolvent evaporated
8. 8
   OtherThe residue was purified by column chromatography

Procedure

To (bromomethyl)cyclobutane (211 mg, 1.42 mmol) in THF (20 mL) was added magnesium (41.3 mg, 1.7 mmol), and initiator iodine (10 mg). The mixture was stirred at rt for 2 hrs, then cooled to −40° C. and added to a solution of Example 21A (100 mg, 0.28 mmol) in THF (20 mL). The mixture was allowed to warm to room temperature, quenched with saturated aqueous NH4Cl, and extracted with EtOAc (2×). The organics were combined, dried (MgSO4), filtered and solvent evaporated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-50% Hexane in ethyl acetate) to afford 63 mg (53%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.62-1.78 (m, 2 H) 1.65 (s, 9 H) 1.76-1.94 (m, 2 H) 1.97-2.18 (m, 4 H) 2.47-2.59 (m, 1 H) 3.92 (s, 3 H) 4.88 (dd, J=8.29, 6.14 Hz, 1 H) 6.93 (d, J=8.90 Hz, 1 H) 7.37 (dd, J=8.90, 3.07 Hz, 1 H) 7.95 (s, 1 H) 8.05 (d, J=2.76 Hz, 1 H); MS (DCI/NH4+) m/z 423 (M+H)+.

Source