Triethylamine → HCID 86666516, compound

HRID 1426367Notes

Reaction equation

HRID 1426367 reaction equation
C(N(CC)CC)C.CS(Cl)(=O)=O.O[CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[N:18]=[C:17]([O:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)[CH:16]=1.[O:39]1[CH2:43][CH2:42][NH:41][C:40]1=[O:44].[H-].[Na+]>C(Cl)Cl>[O:44]=[C:40]1[N:41]([CH2:14][C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:22])[F:23])[N:18]=[C:17]([O:25][CH:26]3[CH2:27][CH2:28][N:29]([C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[CH2:30][CH2:31]3)[CH:16]=2)[CH2:42][CH2:43][O:39]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 739492-OxazolidinoneHCID 67955066HCID 67955066, compound

Product 1

HCID 86666516HCID 86666516, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (220 μL, 1.6 mmol) and then methanesulfonyl chloride (82 μL, 1.1 mmol) were added to a solution of tert-butyl 4-{[4-(hydroxymethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}piperidine-1-carboxylate (0.20 g, 0.53 mmol, from Step 2) in methylene chloride (2 mL) at 0° C. After stirring at this temperature for 30 minutes, the reaction mixture was partitioned between water and EtOAc. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude mesylate intermediate was dissolved in N,N-dimethylformamide (2.0 mL), and oxazolidin-2-one (230 mg, 2.6 mmol) was added. The mixture was cooled to 0° C. and sodium hydride (53 mg, 1.3 mmol, 60% in mineral oil) was added. The reaction was warmed to room temperature and stirred for 40 minutes, then was quenched with water, and extracted with EtOAc. The organic extract was washed with water, brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-70% EtOAc in hexanes afforded product (95 mg, 40%). 1H NMR (400 MHz, CDCl3) δ 7.14 (s, 1H), 6.79 (s, 1H), 5.27 (tt, J=7.7, 4.1 Hz, 1H), 4.44 (s, 2H), 4.44-4.38 (m, 2H), 3.80-3.68 (m, 2H), 3.58-3.47 (m, 2H), 3.31 (ddd, J=13.6, 8.5, 3.6 Hz, 2H), 1.99 (ddt, J=13.2, 6.3, 3.0 Hz, 2H), 1.78-1.67 (m, 2H), 1.47 (s, 9H); 19F NMR (376 MHz, CDCl3) 5-68.89 (s); LCMS (M+Na)+: 468.0.

Workup

  1. customthe reaction mixture was partitioned between water and EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude mesylate intermediate was dissolved in N,N-dimethylformamide (2.0 mL)
  7. temperatureThe reaction was warmed to room temperature
  8. stirringstirred for 40 minutes
  9. customwas quenched with water
  10. extractionextracted with EtOAc
  11. extractionThe organic extract
  12. washwas washed with water, brine
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. washFlash chromatography, eluting with a gradient from 0-70% EtOAc in hexanes afforded product (95 mg, 40%)

Sources & evidence

ORD record
ord-7160341b575e47a594482e7a5b83df58
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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