Cesium carbonate → HCID 57612171, compound

HRID 602711Notes

Reaction equation

HRID 602711 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([C@H:10]([CH:14]2[CH2:17][NH:16][CH2:15]2)[CH:11]([CH3:13])[CH3:12])[CH:6]=[C:7]([F:9])[CH:8]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH:25]([C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=1)[C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][CH:33]=1)[C:29]#[N:30]>C(#N)C>[Cl:40][C:37]1[CH:36]=[CH:35][C:34]([C@H:25]([N:16]2[CH2:15][CH:14]([C@@H:10]([C:5]3[CH:6]=[C:7]([F:9])[CH:8]=[C:3]([F:2])[CH:4]=3)[CH:11]([CH3:13])[CH3:12])[CH2:17]2)[C:26]2[CH:27]=[C:28]([CH:31]=[CH:32][CH:33]=2)[C:29]#[N:30])=[CH:39][CH:38]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 670553513-[Bromo(4-chlorophenyl)methyl]benzonitrileHCID 670658813-[(1S)-1-(3,5-Difluorophenyl)-2-methylpropyl]azetidine--hydrogen chloride (1/1)

Product 1

HCID 57612171HCID 57612171, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 106 mg (0.5 mmole) of 3-[(1S)-1-(3,5-difluorophenyl)-2-methylpropyl]azetidine hydrochloride from Step 3 and 0.650 g (2 mmole) of Cs2CO3 in 5 mL dry acetonitrile was stirred at rt in a flask fitted with a small Dean-Stark trap. After 15 minutes, 0.306 g (1 mmole) of 3-[bromo(4-chlorophenyl)methyl]benzonitrile was added and the mixture was heated at 60° C. After 18 h, the solution was partitioned between ethyl acetate and water. The layers were separated and the organic layer was dried over Na2SO4. The solution was filtered and the filtrate was concentrated to an oil. The residue was purified by chromatography on a Chiralpak-AD column using 4% isopropanol-heptane to afford two enantiomers. Fractions containing the slower product diastereomer were pooled and concentrated to afford the title compound; Mass Spectrum: m/e=451 (M+1, 35Cl) and 453 (M+1, 37Cl).

Workup

  1. customfitted with a small Dean-Stark trap
  2. temperaturethe mixture was heated at 60° C
  3. waitAfter 18 h
  4. customthe solution was partitioned between ethyl acetate and water
  5. customThe layers were separated
  6. dry with materialthe organic layer was dried over Na2SO4
  7. filtrationThe solution was filtered
  8. concentrationthe filtrate was concentrated to an oil
  9. customThe residue was purified by chromatography on a Chiralpak-AD column
  10. customto afford two enantiomers
  11. additionFractions containing the slower product diastereomer
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-41cb7c09bd9f4a859f9796b8a28ce433
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

Loading…