Cesium carbonate → 1-{3-[5-Bromo-2-(5-trifluoromethyl-furan-2-ylmethoxy)-benzyl]-azetidin-1-yl}-2,2,2-trifluoro-ethanone

HRID 237302Notes

Reaction equation

HRID 237302 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:19])=[C:6]([CH:18]=1)[CH2:7][CH:8]1[CH2:11][N:10]([C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH2:9]1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:27][C:28]1[O:29][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:32]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH2:27][C:28]2[O:29][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:32]=2)=[C:6]([CH:18]=1)[CH2:7][CH:8]1[CH2:11][N:10]([C:12](=[O:17])[C:13]([F:15])([F:16])[F:14])[CH2:9]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27946052-(Bromomethyl)-5-(trifluoromethyl)furanHCID 584051121-[3-(5-Bromo-2-hydroxy-benzyl)-azetidin-1-yl]-2,2,2-trifluoro-ethanone

Product 1

HCID 866570631-{3-[5-Bromo-2-(5-trifluoromethyl-furan-2-ylmethoxy)-benzyl]-azetidin-1-yl}-2,2,2-trifluoro-ethanoneYield 91.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-[3-(5-bromo-2-hydroxy-benzyl)-azetidin-1-yl]-2,2,2-trifluoro-ethanone (59 mg, 0.17 mmol) in DMF (10 mL) was added KI (40 mg, 0.24 mmol), Cs2CO3 (170 mg, 0.51 mmol) and 2-bromomethyl-5-trifluoromethyl-furan (56 mg, 0.24 mmol). After 16 h, saturated sodium bicarbonate solution and EtOAc were added. The aqueous portion was extracted three times with EtOAc and the combined organic were dried (Na2SO4) and concentrated. The crude product was purified by RP HPLC (basic conditions) to provide the title compound (76 mg, 91%). MS (ESI): mass calcd. for C18H14BrF6NO3, 486.2; m/z found, 488.1 [M+H]+. 1H NMR (CDCl3): 7.34 (dd, J=8.7, 2.5 Hz, 1H), 7.21 (d, J=2.5 Hz, 1H), 6.89-6.76 (m, 2H), 6.48 (d, J=3.4 Hz, 1H), 5.02 (s, 2H), 4.40 (dd, J=9.6, 8.4 Hz, 1H), 4.22-4.11 (m, 1H), 4.08-4.02 (m, 1H), 3.84 (dd, J=10.7, 5.7 Hz, 1H), 3.11-2.97 (m, 1H), 2.97-2.82 (m, 2H).

Workup

  1. extractionThe aqueous portion was extracted three times with EtOAc
  2. dry with materialthe combined organic were dried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude product was purified by RP HPLC (basic conditions)

Sources & evidence

ORD record
ord-ed2f275d40e14e7789927e4cf81f462d
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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