Lithium diisopropylamide → N-(2,4,5-trifluoro-3-(hydroxy(3-morpholinoquinoxalin-6-yl)methyl)phenyl)pivalamide

HRID 929347Notes

Reaction equation

HRID 929347 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[NH:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13].[Li+].CC([N-]C(C)C)C.[O:25]1[CH2:30][CH2:29][N:28]([C:31]2[CH:32]=[N:33][C:34]3[C:39]([N:40]=2)=[CH:38][C:37]([CH:41]=[O:42])=[CH:36][CH:35]=3)[CH2:27][CH2:26]1>C1COCC1>[F:1][C:2]1[C:7]([CH:41]([OH:42])[C:37]2[CH:38]=[C:39]3[C:34](=[CH:35][CH:36]=2)[N:33]=[CH:32][C:31]([N:28]2[CH2:29][CH2:30][O:25][CH2:26][CH2:27]2)=[N:40]3)=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[NH:10][C:11](=[O:16])[C:12]([CH3:13])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 63372950N-(2,4,5-trifluorophenyl)pivalamideHCID 866771723-Morpholinoquinoxaline-6-carbaldehyde

Product 1

HCID 86677173N-(2,4,5-trifluoro-3-(hydroxy(3-morpholinoquinoxalin-6-yl)methyl)phenyl)pivalamideYield 65.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of N-(2,4,5-trifluorophenyl)pivalamide (550 mg, 2.4 mmol, 1.2 eq.) in THF (30 mL) cooled at −78° C. was added LDA (4.1 mL, 4.8 mmol, 2.4 eq.) dropwise. The resulting mixture was stirred at −78° C. for 1 h, then a solution of 3-morpholinoquinoxaline-6-carbaldehyde (486 mg, 2.0 mol, 1.0 eq.) in THF (20 mL) was added dropwise. The resulting mixture was stirred at −78° C. for 1 h, then quenched by the addition of NH4Cl solution. The mixture was extracted with EA (20 mL×3) and the combined organic layers were dried over Na2SO4 and concentrated. The resulting residue was purified by flash column chromatography (MeOH/DCM=1/50, v/v) to afford N-(2,4,5-trifluoro-3-(hydroxy(3-morpholinoquinoxalin-6-yl)methyl)phenyl)pivalamide (620 mg, 65.2%).

Workup

  1. stirringThe resulting mixture was stirred at −78° C. for 1 h
  2. customquenched by the addition of NH4Cl solution
  3. extractionThe mixture was extracted with EA (20 mL×3)
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. customThe resulting residue was purified by flash column chromatography (MeOH/DCM=1/50

Sources & evidence

ORD record
ord-957b8c57072d49328a4d3ead9f8fa4db
Source dataset
uspto-grants-2016_03
Patent number
US09295671B2

Reaction notes

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