Acetic Acid → HCID 54682298, compound

HRID 356493Notes

Reaction equation

HRID 356493 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13](OC)(=[O:18])[CH2:14][C:15]([CH3:17])=[O:16].[CH2:21]([O:28][C:29]1[CH:30]=[C:31]([CH2:35][CH2:36][C:37](=[O:54])[CH2:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[CH:41]=2)[CH:32]=[CH:33][CH:34]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(O)(=O)C.[OH-].[Na+]>C1COCC1>[CH2:47]([O:46][C:42]1[CH:41]=[C:40]([CH2:39][CH2:38][C:37]2([CH2:36][CH2:35][C:31]3[CH:32]=[CH:33][CH:34]=[C:29]([O:28][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:30]=3)[O:54][C:13](=[O:18])[CH:14]=[C:15]([OH:16])[CH2:17]2)[CH:45]=[CH:44][CH:43]=1)[C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 7757Methyl acetoacetateHCID 7912DiisopropylamineHCID 14798Sodium HydroxideHCID 18798682HCID 18798682, compoundHCID 178418339Butyllithium

Product 1

HCID 54682298HCID 54682298, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 3.3 mL of diisopropylamine (23.5 mmol) in dry THF (500 mL) was cooled to 0° C. under nitrogen, treated with 14.3 mL of 1.64M n-butyllithium (22.8 mmol), and stirred at 0° C. for 25 minutes. To this solution was added 1.2 mL (11.1 mmol) of methyl acetoacetate, and the mixture was stirred for 30 minutes. The solution was then cooled to -78° C. A solution of 5.00 g (11.1 mmol) of 1,5-bis-(3-benzyloxy-phenyl)-pentan-3-one (prepared in Example J) dissolved in dry THF (100 mL) was added dropwise, and the mixture was stirred at low temperature for 3 hours. Dilute acetic acid (2 equivalents) was added, and the mixture was extracted with EtOAc. The extracts were dried (MgSO4) and concentrated. The residue that was obtained was dissolved in THF (250 mL), treated with 0.1N NaOH (500 mL), and stirred overnight at room temperature. The mixture was cooled in an ice bath, quenched with 50% acetic acid, and extracted with EtOAc. The organic layer was dried (MgSO4) and concentrated. The residue was chromatographed on silica gel, eluting with MeOH:CH2Cl2 (2:98), to give 6,6-bis-[2-(3-benzyloxy-phenyl)-ethyl]-5,6-dihydro-4-hydroxy-pyran-2-one. 1H NMR (DMSO-d6) δ 1.93 (m, 4 H), 2.56 (m, 4 H), 3.35 (s, partially obscured by H2O, 2 H), 4.99 (s, 1 H), 5.02 (s, 4 H), 6.72-6.78 (m, 4 H), 6.82 (br s, 2 H), 7.14 (t, 2 H), 7.26-7.39 (m, 10 H).

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. temperatureThe solution was then cooled to -78° C
  3. additionwas added dropwise
  4. stirringthe mixture was stirred at low temperature for 3 hours
  5. extractionthe mixture was extracted with EtOAc
  6. dry with materialThe extracts were dried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue that was obtained
  9. stirringstirred overnight at room temperature
  10. temperatureThe mixture was cooled in an ice bath
  11. customquenched with 50% acetic acid
  12. extractionextracted with EtOAc
  13. dry with materialThe organic layer was dried (MgSO4)
  14. concentrationconcentrated
  15. customThe residue was chromatographed on silica gel
  16. washeluting with MeOH:CH2Cl2 (2:98)

Sources & evidence

ORD record
ord-67ea7f36c7f24c28a4ac65f02428ddc8
Source dataset
uspto-grants-1998_11
Patent number
US05834506

Reaction notes

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