Cesium carbonate → HCID 71204734, compound

HRID 712873Notes

Reaction equation

HRID 712873 reaction equation
[F:1][C:2]1([F:23])[CH2:7][CH2:6][NH:5][C@@H:4]([C:8]([NH:10][C@H:11]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=2)[CH3:12])=[O:9])[CH2:3]1.C([O-])([O-])=O.[Cs+].[Cs+].[F:30][C:31]([F:41])([F:40])[C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Br)=[CH:34][CH:33]=1>CC#N>[F:23][C:2]1([F:1])[CH2:7][CH2:6][N:5]([CH2:36][C:35]2[CH:34]=[CH:33][C:32]([C:31]([F:30])([F:40])[F:41])=[CH:39][CH:38]=2)[C@@H:4]([C:8]([NH:10][C@H:11]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=2)[CH3:12])=[O:9])[CH2:3]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 71204651HCID 71204651, compound

Product 1

HCID 71204734HCID 71204734, compoundYield 20.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of methyl 4-((S)-1-((R)-4,4-difluoropiperidine-2-carboxamido)ethyl)benzoate (D97) (66 mg, 0.20 mmol) in dry MeCN (4 ml), Cs2CO3 (198 mg, 0.60 mmol) and the 4-(Trifluoromethyl)benzylbromide (0.037 ml, 0.24 mmol) were added in sequence and the resulting mixture was stirred at RT for 18 hrs. The solid was filtered off, the acetonitrile was evaporated and the crude was purified by flash chromatography SNAP HP_SiO2 (10 g) eluting with a gradient DCM/EtOAc from 100/0 to 90/10. Collected fractions after solvent evaporation were purified onto reverse phase column GOLD-C18 (15 g) eluting with a gradient of H2O/MeCN (containing 0.1% Acetic acid) from 10/90 to 80/20. Collected fractions after solvent evaporation afforded the title compound (D135) (20 mg).

Workup

  1. filtrationThe solid was filtered off
  2. customthe acetonitrile was evaporated
  3. customthe crude was purified by flash chromatography SNAP HP_SiO2 (10 g)
  4. washeluting with a gradient DCM/EtOAc from 100/0 to 90/10
  5. customCollected fractions after solvent evaporation
  6. customwere purified onto reverse phase column GOLD-C18 (15 g)
  7. washeluting with a gradient of H2O/MeCN (containing 0.1% Acetic acid) from 10/90 to 80/20
  8. customCollected fractions after solvent evaporation

Sources & evidence

ORD record
ord-509cfac8e3e54316992933a7b3acc473
Source dataset
uspto-grants-2015_11
Patent number
US09181279B2

Reaction notes

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