Acetone → HCID 57781094, compound

HRID 1690715Notes

Reaction equation

HRID 1690715 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Li+].CC([N-]C(C)C)C.[CH2:21]([N:23]([CH2:39][CH3:40])[C:24](=[O:38])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH2:31][N:32]1[C:36]([I:37])=[CH:35][N:34]=[CH:33]1)[CH3:22].[CH3:41][C:42]([CH3:44])=[O:43]>C1COCC1.O.C(OCC)(=O)C.C(O)(=O)C>[CH2:39]([N:23]([CH2:21][CH3:22])[C:24](=[O:38])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH:31]([N:32]1[C:36]([I:37])=[CH:35][N:34]=[CH:33]1)[C:42]([OH:43])([CH3:44])[CH3:41])[CH3:40]

Participants

10

Reactant 5

HCID 180AcetoneHCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 57781104HCID 57781104, compoundHCID 178418339Butyllithium

Product 1

HCID 57781094HCID 57781094, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of diisopropylamine (0.97 g, 6.39 mmol) in THF (50 mL) at −78° C. under nitrogen is added n-BuLi (2.5M in hexanes, 3.8 mL, 9.6 mmol) and the mixture is warmed to 0° C. After 15 min, the LDA solution is cooled to −78° C. and a solution of N,N-diethyl-2-(5-iodo-imidazol-1-ylmethyl)-benzamide (2.45 g, 6.39 mmol) (example 1b) in THF (5 mL) is added over 15 min. 30 min after the end of addition, acetone (1.86 g, 31.97 mmol) in THF (5 mL) is added to the brown solution and the mixture is stirred for 1 h, whereupon 10% acetic acid in water is added. The mixture is poured in ethyl acetate and the two phases are separated. The organic phase is washed with saturated aqueous sodium bicarbonate. The combined aqueous phase is extracted twice with ethyl acetate. The combined organic phase is dried over MgSO4, filtered through a cotton plug and concentrated in vacuo. The residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 49:1 to 97:3 to 24:1) to afford U-4478-116 (1.65 g) as a yellow solid; MS (ESI) m/z 442.0 (M+H).

Workup

  1. additionis added to the brown solution
  2. additionis added
  3. customthe two phases are separated
  4. washThe organic phase is washed with saturated aqueous sodium bicarbonate
  5. extractionThe combined aqueous phase is extracted twice with ethyl acetate
  6. dry with materialThe combined organic phase is dried over MgSO4
  7. filtrationfiltered through a cotton plug
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 49:1 to 97:3 to 24:1)
  10. customto afford U-4478-116 (1.65 g) as a yellow solid

Sources & evidence

ORD record
ord-0678a6a1cacb4a7f8420d0fb290acfaf
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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