Methanol → Methyl 2-cyclobutyl-5-iodo-4-methylbenzoate
Reaction equation
[I:1]N1C(=O)CCC1=O.[CH:9]1([C:13]2[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:14]=2[C:15]([O:17][CH3:18])=[O:16])[CH2:12][CH2:11][CH2:10]1.CO>S(=O)(=O)(O)O>[CH:9]1([C:13]2[CH:22]=[C:21]([CH3:23])[C:20]([I:1])=[CH:19][C:14]=2[C:15]([O:17][CH3:18])=[O:16])[CH2:12][CH2:11][CH2:10]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
N-Iodosuccinimide (5.25 g, 23.3 mmol) was added portionwise to a solution of methyl 2-cyclobutyl-4-methylbenzoate (219.2, 4.77 g, 23.3 mmol) in concentrated sulfuric acid (100 ml) at 0° C. The mixture turned very thick after it was stirred at 0° C. for 30 min and at RT for 2 hours. The mixture was cooled to 0° C. again and MeOH (100 ml) was added. The mixture was heated at 60° C. for 2 hours. The methanol was removed under reduced pressure and the residue was poured into ice water (200 ml). The mixture was extracted with EtOAc (2×). The combined organic layers were washed with brine, then aq. 1N NaHCO3, dried (Na2SO4), and concentrated. The residue was purified using column (silica gel) chromatography (hexanes:EtOAc 30:1 to 20:1). Yield: 5.0 g, clear oil, 65%. 1H NMR (400 MHz, Chloroform-d) δ 8.19 (s, 1H), 7.24 (s, 1H), 4.17-4.04 (m, 1H), 3.86 (s, 3H), 2.48-2.44 (s, 3H), 2.40-2.28 (m, 2H), 2.13-1.92 (m, 3H), 1.85-1.75 (m, 1H).
Workup
- temperatureThe mixture was cooled to 0° C. again
- temperatureThe mixture was heated at 60° C. for 2 hours
- customThe methanol was removed under reduced pressure
- additionthe residue was poured into ice water (200 ml)
- extractionThe mixture was extracted with EtOAc (2×)
- washThe combined organic layers were washed with brine
- dry with materialaq. 1N NaHCO3, dried (Na2SO4)
- concentrationconcentrated
- customThe residue was purified
Sources & evidence
- ORD record
- ord-11309ed93ea846c1b98755452f4a64d1
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08871790B2
Reaction notes
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