Cesium carbonate → HCID 11259875, compound

HRID 602696Notes

Reaction equation

HRID 602696 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][NH:16][CH2:15]2)[C:10](F)([CH3:12])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.C([O-])([O-])=[O:19].[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:38]=[CH:39][C:34]([C@H:25]([N:16]2[CH2:17][CH:14]([C@@H:9]([C:4]3[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=3)[C:10]([OH:19])([CH3:12])[CH3:11])[CH2:15]2)[C:26]2[CH:27]=[C:28]([CH:31]=[CH:32][CH:33]=2)[C:29]#[N:30])=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 670553513-[Bromo(4-chlorophenyl)methyl]benzonitrileHCID 670553593-[(1S)-1-(3,5-Difluorophenyl)-2-fluoro-2-methylpropyl]azetidine

Product 1

HCID 11259875HCID 11259875, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A solution of the crude amine from Step 3 and 6.51 g (20 mmole) of Cs2CO3 in 30 mL dry acetonitrile was stirred at rt in a flask fitted with a small Dean-Stark trap. After 15 minutes, 4.6 g (15 mmole) of 3-[bromo(4-chlorophenyl)methyl]benzonitrile was added and the mixture was heated at 60° C. After 18 h, the solution was filtered through CELITE and the residue was washed with acetonitrile. The combined filtrates were concentrated and the residue was purified by flash chromatography using a step gradient of 5 to 20% ethyl acetate-hexane. Fractions containing the faster product diastereomer were pooled and concentrated to afford the title compound; 1NMR (CDCl3) δ 1.25 (t, J=22 Hz, 611), 2.33 (t, J=6.5 Hz, 1H), 2.83-2.89 (m, 2H), 3.09-3.11 (m, 2), 3.60 (m, 1), 4.24 (s, 1H), 6.68-6.71 (m, 3H), 7.21-7.8 (m, 8H); Mass Spectrum: m/e=469 (M+1, 35Cl) and 471 (M+1, 37Cl).

Workup

  1. customfitted with a small Dean-Stark trap
  2. waitAfter 18 h
  3. filtrationthe solution was filtered through CELITE
  4. washthe residue was washed with acetonitrile
  5. concentrationThe combined filtrates were concentrated
  6. customthe residue was purified by flash chromatography
  7. additionFractions containing the faster product diastereomer
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1f8935aeae424b138d93cf619240b1bd
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

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