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

HRID 602678Notes

Reaction equation

HRID 602678 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([O-])([O-])=O.[Cs+].[Cs+]>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][CH:18]([CH: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 10796Cesium carbonateHCID 113805081-[Bromo(phenyl)methyl]-4-chlorobenzeneHCID 67065947Methyl azetidin-3-yl(3,5-difluorophenyl)acetate

Product 1

HCID 86628608Methyl {1-[(4-chlorophenyl)(phenyl)methyl]azetidin-3-yl}(3,5-difluorophenyl)acetate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 0.042 g (0.15 mmol) of 1-[bromo(phenyl)methyl]-4-chlorobenzene, 0.028 g (0.1 mmol) of methyl azetidin-3-yl(3,5-difluorophenyl)acetate (Example 25, Step 1) and 0.298 g (0.3 mmol) of Cs2CO3 in 5 mL of acetonitrile was heated at 45° C. for 18 h. The solution was concentrated and the residue was dissolved in 5 mL of ethyl acetate. This solution was washed with 1 mL water and the aqueous layer was washed with a second aliquot of 3 mL ethyl acetate. The organic extracts were washed with brine, combined, dried over Na2SO4 and concentrated. The residue was purified by chromatography on a Waters RCM column (5 micron silica gel, 20 mm×10 cm) using a 2:1 mixture of hexane and 5:4:1 hexane-methyl tert-butyl ether-acetonitrile. Homogenous fractions were pooled and concentrated to afford the title compound. 1NMR (CDCl3) δ 2.65-2.69 (m, 1H), 2.88-2.93 (m, 1H), 3.05-3.16 (m, 2H), 3.41-3.46 (m, 1H), 3.67 (s, 3H), 3.81-3.86 (m, 1H), 4.30 (s, 1H), 6.69-6.74 (m, 1H), 6.80-6.85 (m, 2H), 7.19-7.37 (m, 9H). Mass Spectrum: m/e=442 (M+1 35Cl) and 444 (M+1 37Cl).

Workup

  1. concentrationThe solution was concentrated
  2. dissolutionthe residue was dissolved in 5 mL of ethyl acetate
  3. washThis solution was washed with 1 mL water
  4. washthe aqueous layer was washed with a second aliquot of 3 mL ethyl acetate
  5. washThe organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on a Waters RCM column (5 micron silica gel, 20 mm×10 cm)
  9. additiona 2:1 mixture of hexane and 5:4:1 hexane-methyl tert-butyl ether-acetonitrile
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-6d69db86f1dd4ec29b12acd07cf8609d
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

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