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

HRID 1478441Notes

Reaction equation

HRID 1478441 reaction equation
[OH:1][CH:2]1[CH:25]=[C:24]([C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[O:23][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]([CH3:22])[CH:13]=3)=[O:11])[CH2:6][CH2:5]2)[CH2:3]1.[CH:32](O)([CH3:34])[CH3:33].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>O>[CH:19]([O:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]([N:7]2[CH2:6][CH2:5][C:4]3([O:23][C:24]([C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)=[CH:25][CH:2]([O:1][CH:32]([CH3:34])[CH3:33])[CH2:3]3)[CH2:9][CH2:8]2)=[O:11])=[CH:13][C:14]=1[CH3:22])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 89704500(4-Hydroxy-2-(pyridin-3-yl)-1-oxa-9-azaspiro[5.5]undec-2-en-9-yl)(4-isopropoxy-3-methylphenyl)methanone

Product 1

HCID 89708519(4-Isopropoxy-3-methyl-phenyl)[8-isopropoxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undec-9-en-3-yl]methanoneYield 52.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

[8-hydroxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undec-9-en-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (300 mg, 0.71 mmol) was dissolved in isopropanol (6.0 mL, 78 mmol). Pyridinium p-toluenesulfonate (178 mg, 0.71 mmol) was added, and the reaction mixture was allowed to stir at 50° C. for 1 hour. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2×50 mL). The organic layers were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (50-75% ethyl acetate/hexane) to provide (4-isopropoxy-3-methyl-phenyl)-[8-isopropoxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undec-9-en-3-yl]methanone (173 mg) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 8.90 (d, J=1.5 Hz, 1H), 8.55 (d, J=3.6 Hz, 1H), 7.90 (dt, J=8.0, 1.9 Hz, 1H), 7.28 (dd, J=7.6, 4.5 Hz, 1H), 7.26-7.17 (m, 2H), 6.82 (d, J=8.2 Hz, 1H), 5.55 (d, J=3.9 Hz, 1H), 4.71-4.27 (m, 2H), 4.19 (dd, J=9.4, 5.3 Hz, 1H), 3.97-3.59 (m, 2H), 3.39 (br s, 2H), 2.40-2.10 (m, 1H), 2.21 (s, 3H), 2.05-1.84 (m, 3H), 1.83-1.49 (m, 2H), 1.33 (t, J=9.8 Hz, 6H), 1.19 (dd, J =6.1, 2.8 Hz, 6H). ESI-MS m/z calc. 464.27, found 465.5 (M+1)+; Retention time: 1.56 minutes (3 min run).

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by column chromatography (50-75% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-87b671cd46b74d26b01bf630bda6b667
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

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