Dimethylformamide → 5-Ethyl-2-fluoro-3-morpholinobenzaldehyde

HRID 2105076Notes

Reaction equation

HRID 2105076 reaction equation
[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([F:15])=[C:7]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:8]=1)[CH3:2].CN(CCN(CCN(C)C)C)C.[Li]CCCC.CN([CH:36]=[O:37])C>C1COCC1>[CH2:1]([C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[C:6]([F:15])=[C:5]([CH:4]=1)[CH:36]=[O:37])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 18196PentamethyldiethylenetriamineHCID 688134234-(5-Ethyl-2-fluorophenyl)morpholineHCID 178418339Butyllithium

Product 1

HCID 862472455-Ethyl-2-fluoro-3-morpholinobenzaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-45 °C

Procedure

To a solution of Intermediate 230.1 (102 mg, 0.487 mmol) and PMDTA (0.132 mL, 0.634 mmol) in 3 mL THF at −78° C., was added BuLi (1.6 M in THF, 0.365 mL, 0.584 mmol). The mixture was allowed to warm to −45° C. over 20 min, then was recooled to −78° C. DMF (75 μL) was added, then the reaction mixture was removed from the cooling bath and stirred 20 min before being quenched with sat. NH4Cl. The mixture was diluted with EtOAc, washed with water and brine, dried (Na2SO4) and concentrated. The crude residue was purified by flash chromatography (0 to 35% EtOAc/hexanes gradient) to afford 77 mg of Intermediate 406.1. LCMS (2 min gradient) RT=1.47 min, 238.18 (M+H)+.

Workup

  1. customwas recooled to −78° C
  2. customthe reaction mixture was removed from the cooling bath
  3. custombefore being quenched with sat. NH4Cl
  4. additionThe mixture was diluted with EtOAc
  5. washwashed with water and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude residue was purified by flash chromatography (0 to 35% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-706d407af66a40d4a3c10cfd6d9749e7
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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