2,6-Dimethylphenol → Ethyl 5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolecarboxylate

HRID 2423454Notes

Reaction equation

[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[OH:9].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:29]1([C:33]2[O:37][N:36]=[C:35]([CH2:38]O)[C:34]=2[C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:32][CH2:31][CH2:30]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1>[CH:29]1([C:33]2[O:37][N:36]=[C:35]([CH2:38][O:9][C:3]3[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=3[CH3:1])[C:34]=2[C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:30][CH2:31][CH2:32]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 2,6-dimethylphenol (503 mg, 4.12 mmol), triphenylphosphine (1.08 g, 4.12 mmol) and ethyl 5-cyclobutyl-3-(hydroxymethyl)-4-isoxazolecarboxylate (929 mg, 4.12 mmol, from multiple batches) in toluene (10 mL) was added diisopropyl azodicarboxylate (0.741 mL, 4.12 mmol) dropwise. The solution was heated in a microwave reactor to 90° C. for 10 minutes. The solution was then concentrated and the residue was purified by chromatography (silica gel, 2.5% acetone in hexanes) to afford ethyl 5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolecarboxylate (1.11 g, 81%). 1H-NMR (400 MHz, DMSO-d6) δ 7.01-6.90 (m, 3H), 5.02 (s, 2H), 4.20 (q, J=7 Hz, 2H), 4.20-4.10 (m, 1H), 2.37-2.30 (m, 4H), 2.14 (s, 6H), 2.11-2.01 (m, 1H), 1.95-1.85 (m, 1H), 1.22 (t, J=7 Hz, 3H).

Workup

concentrationThe solution was then concentrated
customthe residue was purified by chromatography (silica gel, 2.5% acetone in hexanes)

Sources & evidence

ORD record: ord-089ac1aa9f984d8bb2ec05cf5aacacad
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07960552B2

Reaction notes

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