Toluene → (S)-8-(2-azido-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1848541Notes

Reaction equation

HRID 1848541 reaction equation
O[C@H:2]([C:22]1[CH:31]=[CH:30][C:25]2[C:26](=[O:29])[O:27][CH2:28][C:24]=2[C:23]=1[CH3:32])[CH2:3][N:4]1[CH2:21][CH2:20][C:7]2([C:11](=[O:12])[N:10]([C:13]3[CH2:14][O:15][C:16](=[O:19])[C:17]=3[CH3:18])[CH2:9][CH2:8]2)[CH2:6][CH2:5]1.C1(P([N:47]=[N+:48]=[N-:49])(C2C=CC=CC=2)=O)C=CC=CC=1.C1(C)C=CC=CC=1.C1CCN2C(=NCCC2)CC1>ClCCl>[N:47]([C@@H:2]([C:22]1[C:23]([CH3:32])=[C:24]2[C:25](=[CH:30][CH:31]=1)[C:26](=[O:29])[O:27][CH2:28]2)[CH2:3][N:4]1[CH2:21][CH2:20][C:7]2([C:11](=[O:12])[N:10]([C:13]3[CH2:14][O:15][C:16](=[O:19])[C:17]=3[CH3:18])[CH2:9][CH2:8]2)[CH2:6][CH2:5]1)=[N+:48]=[N-:49]

Participants

6

Reactant 4

HCID 1140TolueneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 729500748-[(2R)-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

Product 1

HCID 86709528(S)-8-(2-azido-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
35 °C

Procedure

To a suspension of 8-[(2R)-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 (Example 7, 300 mg, 0.68 mmol) and diphenylphosphoryl azide (578 mg, 1.36 mmol) in a mixed solvent of toluene and dichloromethane (v:v, 10:1, 11 mL) was added DBU (310 mg, 1.36 mmol). The reaction mixture was stirred at 35° C. for 20 h. The solvent was removed by evaporation and the residue was purified by flash column chromatography (0-100% ethyl acetate in petroleum ether gradient) to afford the title compound. 1H NMR (400 MHz, CDCl3): δ 7.32 (d, J=8.0 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 5.20 (s, 2H), 5.18 (s, 2H), 4.94 (dd, J=4.0 Hz, 9.2 Hz, 1H), 3.94 (t, J=6.8 Hz, 2H), 2.88-2.85 (m, 2H), 2.72-2.67 (m, 1H), 2.54-2.50 (m, 1H), 2.42-2.39 (m, 1H), 2.33-2.27 (m, 4H), 2.04 (t, J=6.8 Hz, 2H), 1.95 (s, 3H), 1.94-1.87 (m, 2H), 1.51-1.47 (m, 2H); MS-ESI (m/z): 466 (M+1)+.

Workup

  1. customThe solvent was removed by evaporation
  2. customthe residue was purified by flash column chromatography (0-100% ethyl acetate in petroleum ether gradient)

Sources & evidence

ORD record
ord-ffaa2df515414d45869573849c941b06
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

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