Ammonium formate → (4-Isopropoxy-3-methyl-phenyl)-[10-(1-methylimidazol-2-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone

HRID 713110Notes

Reaction equation

HRID 713110 reaction equation
C([N:8]1[CH2:31][CH:30]([C:32]2[N:33]([CH3:37])[CH:34]=[CH:35][N:36]=2)[O:29][C:10]2([CH2:15][CH2:14][N:13]([C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH3:28])[CH:19]=3)=[O:17])[CH2:12][CH2:11]2)[CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CCO.C(OCC)(=O)C.[OH-].[OH-].[Pd+2]>[CH:25]([O:24][C:21]1[CH:22]=[CH:23][C:18]([C:16]([N:13]2[CH2:14][CH2:15][C:10]3([O:29][CH:30]([C:32]4[N:33]([CH3:37])[CH:34]=[CH:35][N:36]=4)[CH2:31][NH:8][CH2:9]3)[CH2:11][CH2:12]2)=[O:17])=[CH:19][C:20]=1[CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 2

HCID 2723923Ammonium formateHCID 70872859[8-Benzyl-10-(1-methylimidazol-2-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

Product 1

HCID 70872669(4-Isopropoxy-3-methyl-phenyl)-[10-(1-methylimidazol-2-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanoneYield 94%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of [8-benzyl-10-(1-methylimidazol-2-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (50 mg, 0.10 mmol) in EtOH (500 μL) was added Pd(OH)2 (6.98 mg, 0.01 mmol) and ammonium formate (29 mg, 0.46 mmol) and the reaction mixture was heated at 65° C. for 1.5 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, filtered and washed with sat. aq. NaHCO3 (pH 10)/brine. The aqueous was extracted further with ethyl acetate. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give (4-isopropoxy-3-methyl-phenyl)-[10-(1-methylimidazol-2-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone (38 mg, 94%) as a clear colorless oil. ESI-MS m/z calc. 412.2. found 413.3 (M+1)+; Retention time: 1.16 minutes (3 min run).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. washwashed with sat. aq. NaHCO3 (pH 10)/brine
  4. extractionThe aqueous was extracted further with ethyl acetate
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0e9ff746013f465aa66a02dde04b025a
Source dataset
uspto-grants-2015_11
Patent number
US09181273B2

Reaction notes

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