Sodium Bicarbonate → (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(3-fluoroazetidin-1-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 531239Notes

Reaction equation

HRID 531239 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([Br:26])=[CH:24][CH:23]=[C:22](Cl)[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl.[F:32][CH:33]1[CH2:36][NH:35][CH2:34]1.C(=O)(O)[O-].[Na+]>CS(C)=O>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([Br:26])=[CH:24][CH:23]=[C:22]([N:35]4[CH2:36][CH:33]([F:32])[CH2:34]4)[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 101250543-fluoroazetidine HydrochlorideHCID 57576268(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one2×

Product 1

HCID 118021358(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(3-fluoroazetidin-1-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 24, 2.0 g, 3.86 mmol) in DMSO (25 mL), under nitrogen, were added 3-fluoroazetidine hydrochloride (2.16 g, 19.3 mmol) and sodium bicarbonate (1.95 g, 23.2 mmol). The resulting mixture was stirred at 150° C. overnight. The reaction mixture was quenched with water, then extracted 3 times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate in hexanes to afford the titled compound. 1H NMR (500 MHz, CDCl3): δ 7.92 (s, 1H); 7.81 (s, 2H); 7.60 (d, J=8.5 Hz, 1H); 6.20 (d, J=8.6 Hz, 1H); 5.79 (d, J=8.6 Hz, 1H); 5.52 (m, 0.5H); 5.40 (m, 0.5H); 4.90 (d, J=16.9 Hz, 1H); 4.40-4.24 (m, 4H); 4.20-4.09 (m, 2H); 0.82 (d, J=6.6 Hz, 3H).

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted 3 times with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with ethyl acetate in hexanes

Sources & evidence

ORD record
ord-2b9c1ca0bcd44efca20ab325170fa8ae
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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