4-Methylmorpholine → HCID 24764639, compound

HRID 2112801Notes

Reaction equation

HRID 2112801 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](CC(O)=O)=[CH:3][CH:2]=1.[C:11]([C:15]1[CH:20]=[CH:19][C:18]([S:21]([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)(=[O:23])=[O:22])=[CH:17][CH:16]=1)([CH3:14])([CH3:13])[CH3:12].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.O.ON1C2C=CC=CC=2N=N1.CN1CC[O:69][CH2:68][CH2:67]1>C([O-])(O)=O.[Na+].CN(C=O)C>[C:11]([C:15]1[CH:16]=[CH:17][C:18]([S:21]([N:24]2[CH2:29][CH2:28][N:27]([C:68](=[O:69])[CH2:67][C:6]3[CH:5]=[CH:4][CH:3]=[CH:2][N:1]=3)[CH2:26][CH2:25]2)(=[O:23])=[O:22])=[CH:19][CH:20]=1)([CH3:14])([CH3:12])[CH3:13]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 342284-Pyridineacetic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27960291-Hydroxybenzotriazole hydrateHCID 29298041-[(4-tert-butylphenyl)sulfonyl]piperazine

Product 1

HCID 24764639HCID 24764639, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A 25 mL flask was charged with 60 mg 2-(pyridin-4-yl)acetic acid (0.35 mmol, 1.0 equiv), 150 mg 1-(4-tert-butylphenylsulfonyl)piperazine (0.53 mmol, 1.5 equiv), 378 mg O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 0.88 mmol, 2.1 equiv), and 119 mg 1-hydroxybenzotriazole hydrate (HOBT, 0.88 mmol, 2.1 equiv). The flask was then charged with 5 mL DMF, stirring was initiated (magnetic stirrer) and 0.97 mL N-methylmorpholine (NMM, 0.88 mmol, 2.1 equiv) was added in one portion to the suspension. After 12 h, the suspension was diluted with 20 mL sat. NaHCO3 and extracted (2×CH2Cl2). The CH2Cl2 solution was then dried (Na2SO4) and concentrated under reduced pressure. Purification by flash chromatography (SiO2, 0-5% MeOH/CH2Cl2) gave the product as a white solid: 1H NMR (CDCl3, 400 MHz) δ 8.50 (d, J=5.2 Hz, 2 H), 7.70 (d, J=8.5 Hz, 2 H), 7.55 (d, J=8.5 Hz, 2 H), 7.09 (d, J=5.3 Hz, 2 H), 3.73 (m, 2 H), 3.65 (s, 2H), 3.53 (m, 2H), 2.99 (m, 2H), 2.89 (m, 2H), 1.36 (s, 3 H).

Workup

  1. additionwas added in one portion to the suspension
  2. extractionextracted (2×CH2Cl2)
  3. dry with materialThe CH2Cl2 solution was then dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash chromatography (SiO2, 0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-38711e8ab11747c981bffa2b0e19d636
Source dataset
uspto-grants-2009_04
Patent number
US07524848B2

Reaction notes

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