Methyl iodide → (4-Isopropoxy-3-methoxy-phenyl)-[cis-8-methoxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]methanone

HRID 1478432Notes

Reaction equation

HRID 1478432 reaction equation
[OH:1][C@H:2]1[CH2:26][C@@H:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:24][C:4]2([CH2:9][CH2:8][N:7]([C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH:19]([CH3:21])[CH3:20])=[C:14]([O:22][CH3:23])[CH:13]=3)=[O:11])[CH2:6][CH2:5]2)[CH2:3]1.[H-].[Na+].IC.[C:37](OCC)(=O)C>CN(C=O)C.O>[CH:19]([O:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]([N:7]2[CH2:8][CH2:9][C:4]3([O:24][C@H:25]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH2:26][C@H:2]([O:1][CH3:37])[CH2:3]3)[CH2:5][CH2:6]2)=[O:11])=[CH:13][C:14]=1[O:22][CH3:23])([CH3:20])[CH3:21]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 117772949[cis-8-Hydroxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methoxy-phenyl)methanone

Product 1

HCID 117772720(4-Isopropoxy-3-methoxy-phenyl)-[cis-8-methoxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]methanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of [cis-8-hydroxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methoxy-phenyl)methanone (139 mg, 0.3 mmol) in DMF (4 mL) was added sodium hydride (34 mg, 1.5 mmol). The mixture was stirred at room temperature for 30 minutes. Iodomethane (187 μL, 3.00 mmol) was added. The mixture was stirred at room temperature overnight, then repartitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were washed with water (3×), brine, dried over MgSO4, filtered and concentrated to dryness. The crude material was purified by column chromatography (50-60% ethyl acetate-Hex) to provide (4-isopropoxy-3-methoxy-phenyl)-[cis-8-methoxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]methanone (102 mg). 1H NMR (400 MHz, CDCl3) δ 7.48-7.33 (m, 4H), 7.33-7.28 (m, 1H), 7.01-6.90 (m, 2H), 6.86 (d, J=8.2 Hz, 1H), 4.66-4.46 (m, 2H), 4.12-3.90 (m, 2H), 3.86 (s, 3H), 3.76-3.61 (m, 1H), 3.48 (s, 1H), 3.37 (d, J=4.5 Hz, 3H), 3.21 (t, J=11.8 Hz, 1H), 2.28 (dd, J=39.8, 13.2 Hz, 2H), 2.00 (dd, J=12.6, 2.7 Hz, 1H), 1.85-1.62 (m, 3H), 1.59-1.44 (m, 1H), 1.42-1.33 (m, 7H). ESI-MS m/z calc. 453.25, found 454.5 (M+1)+; Retention time: 1.65 minutes (3 minute run).

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  3. washThe combined organic layers were washed with water (3×), brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude material was purified by column chromatography (50-60% ethyl acetate-Hex)

Sources & evidence

ORD record
ord-f96c0d44ca634305af6d06b078647352
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

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