Ethyl 5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carboxylate → 4-{4-[(1-{[5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]carbonyl}azetidin-3-yl)oxy]-3-methylbenzyl}morpholine

HRID 1035178Notes

Reaction equation

[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:18]=[CH:17][C:9]([CH2:10][N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:8][C:7]=2[CH3:19])[CH2:2]1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[O:32][C:31]([C:33](OCC)=[O:34])=[N:30][N:29]=2)=[CH:24][CH:23]=1>C(O)C>[CH3:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[O:32][C:31]([C:33]([N:1]3[CH2:4][CH:3]([O:5][C:6]4[CH:18]=[CH:17][C:9]([CH2:10][N:11]5[CH2:12][CH2:13][O:14][CH2:15][CH2:16]5)=[CH:8][C:7]=4[CH3:19])[CH2:2]3)=[O:34])=[N:30][N:29]=2)=[CH:26][CH:27]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 12B (0.18 g, 0.69 mmol) and ethyl 5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carboxylate (0.19 g, 0.75 mmol) was heated to 120° C. for 3 h using an oil-bath. Ethanol (0.1 mL) was added and the mixture was further heated to 120° C. for 30 min. The product was purified by column chromatography eluting with DCM and then with MeOH/DCM (0.5-2%). There was obtained 0.23 g (71%) of 12 as a solid. 1H NMR (600 MHz, CDCl3): δ 2.22 (s, 3H), 2.33-2.50 (m, 4H), 3.39 (s, 2H) 3.60-3.77 (m, 4H), 3.86 (s, 3H), 4.26-4.36 (m, 1H), 4.57-4.78 (m, 2H), 4.99-5.16 (m, 2H), 6.42 (d, 1H), 6.99 (d, 2H), 7.05 (d, 1H), 7.12 (s, 1H), 8.07 (d, 2H), MS (APCI+) m/z 465 [M+H]+, LC purity: 99%.

Workup

temperaturethe mixture was further heated to 120° C. for 30 min
customThe product was purified by column chromatography
washeluting with DCM

Sources & evidence

ORD record: ord-1d4044c7beb14f4cb0bf8f30e324affa
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546375B2

Reaction notes

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