Diisopropylethylamine → Methyl {1-[(4-chlorophenyl)(phenyl)methyl]azetidin-3-ylidene}(3,5-difluorophenyl)acetate

HRID 602673Notes

Reaction equation

HRID 602673 reaction equation
Br[CH:2]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][CH:4]=1.[NH:16]1[CH2:19][CH:18]([CH:20]([C:25]2[CH:30]=[C:29]([F:31])[CH:28]=[C:27]([F:32])[CH:26]=2)[C:21]([O:23][CH3:24])=[O:22])[CH2:17]1.C(N(C(C)C)CC)(C)C>C(#N)C>[Cl:9][C:6]1[CH:7]=[CH:8][C:3]([CH:2]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:16]2[CH2:19][C:18](=[C:20]([C:25]3[CH:30]=[C:29]([F:31])[CH:28]=[C:27]([F:32])[CH:26]=3)[C:21]([O:23][CH3:24])=[O:22])[CH2:17]2)=[CH:4][CH:5]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 113805081-[Bromo(phenyl)methyl]-4-chlorobenzeneHCID 67065947Methyl azetidin-3-yl(3,5-difluorophenyl)acetate

Product 1

HCID 67065891Methyl {1-[(4-chlorophenyl)(phenyl)methyl]azetidin-3-ylidene}(3,5-difluorophenyl)acetate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 0.280 g (1 mmol) of 1-[bromo(phenyl)methyl]4-chlorobenzene, 0.120 g (0.5 mmol) of methyl azetidin-3-yl(3,5-difluorophenyl)acetate (Example 22, Step 1) and 0.12 mL (0.7 mmol) of diisopropylethylamine in 10 mL of acetonitrile was heated at 40° C. for 18 h. The solution was concentrated and the residue was dissolved in 20 mL of ethyl acetate. This solution was washed with 10 mL water and the aqueous layer was washed with a second aliquot of 20 mL ethyl acetate. The organic extracts were washed with brine, combined, and concentrated. The residue was dissolved in acetonitrile and purified by reverse phase chromatography (Waters Xterra C18, 19 mm×50 mm) using a gradient of acetonitrile-water-triethylamine (30:70:1 to 60:40:1) to afford the title compound; 1NMR (CDCl3) δ 3.74 (s, 3H), 3.88 (m, 2H), 4.24 (m, 2H), 4.55 (s, 1H), 6.70-6.86 (m, 3H), 7.21-7.43 (m, 911); Mass Spectrum: m/e=440 (M+1 35Cl) and 442 (M+1 37Cl).

Workup

  1. concentrationThe solution was concentrated
  2. dissolutionthe residue was dissolved in 20 mL of ethyl acetate
  3. washThis solution was washed with 10 mL water
  4. washthe aqueous layer was washed with a second aliquot of 20 mL ethyl acetate
  5. washThe organic extracts were washed with brine
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in acetonitrile
  8. custompurified by reverse phase chromatography (Waters Xterra C18, 19 mm×50 mm)

Sources & evidence

ORD record
ord-0d6514ac3aa34363927202c145134085
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

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