Diisopropylamine → HCID 57781123, compound

HRID 1690714Notes

Reaction equation

HRID 1690714 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].[C:41]1(=[O:45])[CH2:44][CH2:43][CH2:42]1>C1COCC1.O.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]([C:41]1([OH:45])[CH2:44][CH2:43][CH2:42]1)[N:32]1[C:36]([I:37])=[CH:35][N:34]=[CH:33]1)[CH3:40]

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 14496CyclobutanoneHCID 2724682Lithium diisopropylamideHCID 57781104HCID 57781104, compoundHCID 178418339Butyllithium

Product 1

HCID 57781123HCID 57781123, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of diisopropylamine (0.38 g, 3.76 mmol) in THF (25 mL) at −78° C. under nitrogen is added n-BuLi (2.5M in hexanes, 1.50 mL, 3.75 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 (1.00 g, 2.51 mmol) in THF (5 mL) is added over 10 min. Fifteen min after the end of addition, cyclobutanone (0.90 g, 12.53 mmol) in THF (2 mL) is added to the brown solution. After 1.5 h, 10% acetic acid in water is added. The organic phase is washed with saturated aqueous sodium bicarbonate and 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 N,N-diethyl-2-[(1-hydroxy-cyclobutyl)-(5-iodo-imidazol-1-yl)-methyl]-benzamide; MS (ESI) m/z 454.2 (M+H).

Workup

  1. additionis added to the brown solution
  2. waitAfter 1.5 h
  3. washThe organic phase is washed with saturated aqueous sodium bicarbonate
  4. dry with materialthe combined organic phase is dried over MgSO4
  5. filtrationfiltered through a cotton plug
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 49:1 to 97:3) to N,N-diethyl-2-[(1-hydroxy-cyclobutyl)-(5-iodo-imidazol-1-yl)-methyl]-benzamide

Sources & evidence

ORD record
ord-4058a074a467491583c41af81e2f9e93
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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