Hydrochloric Acid → Methyl 5-acetyl-4-cyclobutyl-2-methylbenzoate

HRID 541392Notes

Reaction equation

[CH:1]1([C:5]2[C:14](I)=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([CH3:16])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[CH:17]([O:19]CCCC)=[CH2:18].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl>CS(C)=O.O.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:17]([C:14]1[C:5]([CH:1]2[CH2:4][CH2:3][CH2:2]2)=[CH:6][C:7]([CH3:16])=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10])(=[O:19])[CH3:18]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of methyl 4-cyclobutyl-5-iodo-2-methylbenzoate (152.3, 5.00 g, 15.1 mmol, 1.00 equiv) in DMSO (50 mL) under nitrogen were added 1-(ethenyloxy)butane (3.03 g, 30.3 mmol, 2.00 equiv), DPPP (624 mg, 1.51 mmol, 0.10 equiv), Pd(OAc)2 (324 mg, 1.51 mmol, 0.10 equiv), and TEA (3.06 g, 30.2 mmol, 2.00 equiv). The resulting mixture was stirred overnight at 120° C. under nitrogen, then cooled to ambient temperature and diluted with water. The pH was adjusted to 1 with hydrogen chloride (aq., 6 M). The resulting mixture was diluted with 200 mL of ethyl acetate, washed with brine (3×200 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:30) as eluent to furnish 2.28 g (61%) of the title compound as a yellow oil.

Workup

temperaturecooled to ambient temperature
washwashed with brine (3×200 mL)
dry with materialdried (Na2SO4)
concentrationconcentrated under reduced pressure
customThe residue was purified

Sources & evidence

ORD record: ord-80e9795df5f04eb1bea2b9a4f49ba6b0
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871790B2

Reaction notes

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