Dimethyl Sulfoxide → 6-(1,1-Dimethylethyl) 1-ethyl 6-azaspiro[2.5]octane-1,6-dicarboxylate

HRID 520330Notes

Reaction equation

HRID 520330 reaction equation
[H-].[Na+].CS(C)=O.[I-].[CH3:8][S+](C)(C)=O.[CH2:13]([O:15][C:16](=[O:31])[CH:17]=[C:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1)[CH3:14]>O>[CH:17]1([C:16]([O:15][CH2:13][CH3:14])=[O:31])[C:18]2([CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH2:8]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 10333298tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate

Product 1

HCID 497574526-(1,1-Dimethylethyl) 1-ethyl 6-azaspiro[2.5]octane-1,6-dicarboxylateYield 54.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
15 °C

Procedure

Sodium hydride (60% in mineral oil) (2.06 g, 85.8 mmol) was added to dimethylsulfoxide (100 mL) at 15° C., and the mixture was stirred at 15° C. for 20 min. See FIG. 6. Trimethylsulfoxonium iodide (19.0 g, 85.8 mmol) was added, and the reaction mixture was stirred for 2 h, then 165b (7.72 g, 28.7 mmol) was added and the resulting mixture was stirred at 15° C. for 50 h. Water (100 mL) was added, and the mixture was extracted with EtOAc (200 mL×3). The combined organic extracts were washed with brine (100 mL×2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column (petroleum ether: EtOAc=2:1) to yield 6-tert-butyl 1-ethyl 6-azaspiro[2.5]octane-1,6-dicarboxylate 165c (4.4 g, 54%) as a colorless oil. 1H NMR (400 MHz, CD3CN): δ 4.06-4.04 (m, 2H), 3.40-3.18 (m, 4H), 1.92-1.90 (m, 1H), 1.59-1.50 (m, 3H), 1.39-1.30 (m, 10H), 1.19-1.16 (m, 3H), 1.03-1.01 (m, 1H), 0.91-0.93 (m, 1H).

Workup

  1. stirringthe reaction mixture was stirred for 2 h
  2. stirringthe resulting mixture was stirred at 15° C. for 50 h
  3. extractionthe mixture was extracted with EtOAc (200 mL×3)
  4. washThe combined organic extracts were washed with brine (100 mL×2)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column (petroleum ether: EtOAc=2:1)

Sources & evidence

ORD record
ord-12506f4cc3d74da3bb39b59c6307f5af
Source dataset
uspto-grants-2016_05
Patent number
US09326985B2

Reaction notes

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