Tetrahydrofuran → HCID 59238593, compound

HRID 1924477Notes

Reaction equation

HRID 1924477 reaction equation
[CH2:1]1[O:11][C:4]2([CH2:9][CH2:8][C:7](=O)[CH2:6][CH2:5]2)[O:3][CH2:2]1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.N1C=[CH:21]N=N1.C[Mg]Cl.C1COCC1.[NH4+].[Cl-]>C1(C)C=CC=CC=1.CCOCC>[CH3:21][C:7]1([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH2:8][CH2:9][C:4]2([O:11][CH2:1][CH2:2][O:3]2)[CH2:5][CH2:6]1

Participants

9

Reactant 6

HCID 8028TetrahydrofuranHCID 8083MorpholineHCID 25517Ammonium ChlorideHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 178418332HCID 178418332, compoundHCID 178418936HCID 178418936, compound

Product 1

HCID 59238593HCID 59238593, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of 1,4-cyclohexanedione monoethylene acetal (7.81 g, 50.00 mmol), morpholine (4.81 mL, 55 mmol) and 1H-1,2,3-triazole (3.48 mL, 60 mmol) in toluene (50 mL) was refluxed for 6 hours while collecting water using a Dean-Stark apparatus. The white suspension containing 10 was allowed to cool to RT and added dropwise over 1 hour to a cooled (ice/salt/water bath) 3.0 M MeMgCl solution in THF (66.67 mL, 200 mmol) while maintaining the internal temperature <24° C. The reaction mixture was stirred at RT for a further 2 h. The mixture was then diluted with Et2O (500 mL). An aqueous solution of NH4Cl was added in portions until a precipitate formed. The organic layer was decanted off, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by SGC on amino silica (Chromatorex NH, Fuji Silysia) using hexane:EtOAc as eluent (gradient elution from 100:0 to 50:50, v/v) to give 11 (10.94 g, 91%) as a yellowish white solid. 1H NMR (400 MHz, CDCl3) δ 0.89 (s, 3H), 1.41-1.48 (m, 4H), 1.80-1.94 (m, 4H), 2.50 (t, J=4.2 Hz, 4H), 3.70 (t, J=4.6 Hz, 4H), 3.95 (app. t, J=1.7 Hz, 4H).

Workup

  1. temperaturewas refluxed for 6 hours
  2. customwhile collecting water using a Dean-Stark apparatus
  3. additionThe white suspension containing 10
  4. additionadded dropwise over 1 hour to
  5. temperaturewhile maintaining the internal temperature <24° C
  6. customformed
  7. customThe organic layer was decanted off
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by SGC on amino silica (Chromatorex NH, Fuji Silysia)
  12. washEtOAc as eluent (gradient elution from 100:0 to 50:50

Sources & evidence

ORD record
ord-bf6016adf1de4413a3b7f32c00276ecb
Source dataset
uspto-grants-2012_05
Patent number
US08178552B2

Reaction notes

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