(4-Isopropoxy-3-methyl-phenyl)[8-isopropoxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undec-9-en-3-yl]methanone → (4-Isopropoxy-3-methyl-phenyl)-[cis-8-isopropoxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undecan-3-yl]methanone

HRID 1478442Notes

Reaction equation

HRID 1478442 reaction equation
[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([N:13]2[CH2:18][CH2:17][C:16]3([O:23][C:22]([C:24]4[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=4)=[CH:21][CH:20]([O:30][CH:31]([CH3:33])[CH3:32])[CH2:19]3)[CH2:15][CH2:14]2)=[O:12])=[CH:7][C:6]=1[CH3:34])([CH3:3])[CH3:2]>C(O)C.[Pd]>[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([N:13]2[CH2:18][CH2:17][C:16]3([O:23][C@H:22]([C:24]4[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=4)[CH2:21][C@H:20]([O:30][CH:31]([CH3:33])[CH3:32])[CH2:19]3)[CH2:15][CH2:14]2)=[O:12])=[CH:7][C:6]=1[CH3:34])([CH3:3])[CH3:2]

Participants

4

Reactant 1

HCID 89708519(4-Isopropoxy-3-methyl-phenyl)[8-isopropoxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undec-9-en-3-yl]methanone

Product 1

HCID 117772921(4-Isopropoxy-3-methyl-phenyl)-[cis-8-isopropoxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undecan-3-yl]methanoneYield 17.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of (4-isopropoxy-3-methyl-phenyl)[8-isopropoxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undec-9-en-3-yl]methanone (163 mg, 0.35 mmol) in ethanol (10 mL) under nitrogen was added palladium (37 mg, 0.035 mmol) (10 wt % on carbon, wet). The reaction was purged with hydrogen gas and allowed to stir under a balloon of hydrogen overnight. The reaction mixture was filtered through a pad of celite. The filtrate was concentrated under reduced pressure. The reaction mixture was purified by column chromatography (50-100% ethyl acetate/hexane) to provide (4-isopropoxy-3-methyl-phenyl)-[cis-8-isopropoxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undecan-3-yl]methanone (28.7 mg) as a clear colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.62 (s, 1H), 8.54 (d, J=3.9 Hz, 1H), 7.73 (d, J=7.8 Hz, 1H), 7.37-7.24 (m, 1H), 7.22-7.13 (m, 2H), 6.80 (d, J=8.1 Hz, 1H), 4.65-4.50 (m. 1H), 4.55 (dp, J=12.2, 6.1 Hz, 1H), 4.36 (br s, 1H), 3.85 (s, 1H), 3.76 (dt, J=12.1, 6.1 Hz, 1H), 3.70-3.01 (m, 3H), 2.25 (m, 2H), 2.19 (s, 3H), 1.95 (dd, J=12.8, 2.9 Hz, 1H), 1.84-1.37 (m, 5H), 1.34 (d, J=6.0 Hz, 6H), 1.16 (dd, J=6.0, 3.6 Hz, 6H). ESI-MS m/z calc. 466.28, found 467.6 (M+1)+; Retention time: 1.41 minutes (3 min run).

Workup

  1. customThe reaction was purged with hydrogen gas
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customThe reaction mixture was purified by column chromatography (50-100% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9ecfa2b73408446f9910df0a8f5927b7
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

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