Iodoethane → [10-(Ethoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

HRID 713118Notes

Reaction equation

HRID 713118 reaction equation
Cl.C([N:9]1[CH2:32][CH:31]([CH2:33][OH:34])[O:30][C:11]2([CH2:16][CH2:15][N:14]([C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH3:29])[CH:20]=3)=[O:18])[CH2:13][CH2:12]2)[CH2:10]1)C1C=CC=CC=1.[H-].[Na+].I[CH2:38][CH3:39].C([O-])=O.[NH4+]>CN(C=O)C.CCOC(C)=O.CO.[Pd]>[CH2:38]([O:34][CH2:33][CH:31]1[O:30][C:11]2([CH2:16][CH2:15][N:14]([C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH3:29])[CH:20]=3)=[O:18])[CH2:13][CH2:12]2)[CH2:10][NH:9][CH2:32]1)[CH3:39]

Participants

9

Reactant 4

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 2723923Ammonium formateHCID 70872821HCID 70872821, compound

Product 1

HCID 70873081[10-(Ethoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanoneYield 74%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To [8-benzyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone hydrochloride salt (43 mg, 0.09 mmol) in DMF (0.5 mL) was added sodium hydride (11 mg, 0.30 mmol) and the reaction mixture was stirred for 20 minutes. Iodoethane (30 μL, 0.38 mmol) was added and the reaction mixture was stirred for 3 hours, then diluted with EtOAc, filtered, concentrated in vacuo. The residue was purified by silica gel column chromatography using 10-100 EtOAc/hexanes eluent to give the ether intermediate as pale yellow oil. The oil was dissolved in methanol (0.6 mL), and Pd (5 mg, 0.004 mmol) and ammonium formate (27 mg, 0.44 mmol) were added and the reaction mixture was heated at 75° C. for 40 minutes. The reaction mixture was filtered, concentrated in vacuo, diluted with ethyl acetate, washed with 1:1 3M NaOH/sat. aq. NaHCO3, dried over MgSO4, filtered and concentrated in vacuo to give [10-(ethoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (25 mg, 74%) as a pale yellow oil. ESI-MS m/z calc. 390.5. found 391.3 (M+1)+; Retention time: 1.17 minutes (3 min run).

Workup

  1. stirringthe reaction mixture was stirred for 3 hours
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel column chromatography
  5. customto give the ether intermediate as pale yellow oil
  6. filtrationThe reaction mixture was filtered
  7. concentrationconcentrated in vacuo
  8. additiondiluted with ethyl acetate
  9. washwashed with 1:1 3M NaOH/
  10. dry with materialaq. NaHCO3, dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e82e7de5be554da08de64745c5c5cfd0
Source dataset
uspto-grants-2015_11
Patent number
US09181273B2

Reaction notes

Loading…