Triphenylphosphine → 4-(5-Methyl-pyridin-2-ylmethoxy)-1-{2-[3-(2,2,2-trifluoro-acetyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-ethyl}-1H-pyridin-2-one

HRID 564176Notes

Reaction equation

HRID 564176 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][N:5]([CH2:8][CH2:9][C:10]2[CH:26]=[CH:25][C:13]3[CH2:14][CH2:15][N:16]([C:19](=[O:24])[C:20]([F:23])([F:22])[F:21])[CH2:17][CH2:18][C:12]=3[CH:11]=2)[C:4](=[O:27])[CH:3]=1.[CH3:28][C:29]1[CH:30]=[CH:31][C:32]([CH2:35]O)=[N:33][CH:34]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C(Cl)Cl>[CH3:28][C:29]1[CH:30]=[CH:31][C:32]([CH2:35][O:1][C:2]2[CH:7]=[CH:6][N:5]([CH2:8][CH2:9][C:10]3[CH:26]=[CH:25][C:13]4[CH2:14][CH2:15][N:16]([C:19](=[O:24])[C:20]([F:21])([F:22])[F:23])[CH2:17][CH2:18][C:12]=4[CH:11]=3)[C:4](=[O:27])[CH:3]=2)=[N:33][CH:34]=1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 12325387(5-Methylpyridin-2-yl)methanolHCID 598220864-Hydroxy-1-{2-[3-(2,2,2-trifluoro-acetyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-ethyl}-1H-pyridin-2-one

Product 1

HCID 580427394-(5-Methyl-pyridin-2-ylmethoxy)-1-{2-[3-(2,2,2-trifluoro-acetyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-ethyl}-1H-pyridin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To 320 mg (0.84 mmol) 4-hydroxy-1-{2-[3-(2,2,2-trifluoro-acetyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-ethyl}-1H-pyridin-2-one (preparation 21b) in 25 mL DCM is added 129 mg (1.05 mmol) (5-methyl-pyridin-2-yl)-methanol and 221 mg (0.84 mmol) triphenylphosphane. The reaction mixture is cooled to 0° C. and 174 μL (0.84 mmol) diisopropyl azodicarboxylate is added. The reaction mixture is stirred 16 h at RT and then additional 221 mg (0.84 mmol) triphenylphosphane and 174 μL (0.84 mmol) diisopropyl azodicarboxylate is added. The mixture is stirred 2 h at RT, the solvent is evaporated and to the residue water is added. The aqueous phase is extracted with DCM, dried over Na2SO4 and the solvent is evaporated. The residue is purified via reverse HPLC chromatography (Zorbax stable bond, C18; water (0.1% formic acid)/acetonitrile (0.1% formic acid) 95:5 to 5:95).

Workup

  1. stirringThe mixture is stirred 2 h at RT
  2. customthe solvent is evaporated and to the residue water
  3. additionis added
  4. extractionThe aqueous phase is extracted with DCM
  5. dry with materialdried over Na2SO4
  6. customthe solvent is evaporated
  7. customThe residue is purified via reverse HPLC chromatography (Zorbax stable bond, C18; water (0.1% formic acid)/acetonitrile (0.1% formic acid) 95:5 to 5:95)

Sources & evidence

ORD record
ord-7dae94fc32334c07987c1d974f56589f
Source dataset
uspto-grants-2011_11
Patent number
US08067590B2

Reaction notes

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