(S)-4-methyl-5-(oxiran-2-yl)isobenzofuran-1(3H)-one → 8-[(2S)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1848535Notes

Reaction equation

[CH3:1][C:2]1[C:6](=[O:7])[O:5][CH2:4][C:3]=1[N:8]1[CH2:12][CH2:11][C:10]2([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[C:9]1=[O:18].[CH3:19][C:20]1[C:28]([C@H:29]2[CH2:31][O:30]2)=[CH:27][CH:26]=[C:25]2[C:21]=1[CH2:22][O:23][C:24]2=[O:32]>C(O)C>[OH:30][C@@H:29]([C:28]1[CH:27]=[CH:26][C:25]2[C:24](=[O:32])[O:23][CH2:22][C:21]=2[C:20]=1[CH3:19])[CH2:31][N:15]1[CH2:16][CH2:17][C:10]2([C:9](=[O:18])[N:8]([C:3]3[CH2:4][O:5][C:6](=[O:7])[C:2]=3[CH3:1])[CH2:12][CH2:11]2)[CH2:13][CH2:14]1

Participants

Conditions

Temperature: 140 °C

Procedure

To a solution of 2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one (I-17, 10 mg, 0.040 mmol) in ethanol (2 mL) in a microwave tube was added (S)-4-methyl-5-(oxiran-2-yl)isobenzofuran-1(3H)-one (I-4A, 9.9 mg, 0.052 mmol)) and the resulting solution was heated at 140° C. in microwave for 3 h. After concentration, the residue was purified by preparative TLC using 30% methanol/ethyl acetate to give the title compound. LC/MS, (M+1)+: 441.00, 1HNMR (500 MHz, CDCl3), δ7.840-7.804 (m, 2H), 5.304-5.240 (m, 4H), 5.134-5.107 (m, 1H), 4.066-4.038 (t, J=7.1 Hz, 2H), 3.185-3.161 (m, 1H), 2.8885-2.862 (m, 1H), 2.629-2.568 (m, 2H), 2.462-2.416 (m, 1H), 2.305 (s, 3H), 2.344-2.323 (m, 1H), 2.197-2.158 (t, J=7.1 Hz, 2H), 2.108-2.033 (m, 5H), 1.661-1.604 (m, 2H).

Workup

concentrationAfter concentration
customthe residue was purified by preparative TLC

Sources & evidence

ORD record: ord-14acf595418846578e4f4ef26c361a55
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952166B2

Reaction notes

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