4-Methylmorpholine → HCID 22004968, compound

HRID 324817Notes

Reaction equation

HRID 324817 reaction equation
[CH:1]([C:4]1[C:9]([CH2:10]Br)=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:7]([CH2:19][O:20][Si](C(C)(C)C)(C)C)=[C:6]([CH:28]([CH3:30])[CH3:29])[N:5]=1)([CH3:3])[CH3:2].[N+:31]([C:34]1[CH:39]=[CH:38][C:37]([SH:40])=[CH:36][CH:35]=1)([O-:33])=[O:32].CN1CCOCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH:28]([C:6]1[C:7]([CH2:19][OH:20])=[C:8]([C:12]2[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=2)[C:9]([CH2:10][S:40][C:37]2[CH:38]=[CH:39][C:34]([N+:31]([O-:33])=[O:32])=[CH:35][CH:36]=2)=[C:4]([CH:1]([CH3:3])[CH3:2])[N:5]=1)([CH3:29])[CH3:30]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 158094-NitrobenzenethiolHCID 2724141Tetrabutylammonium FluorideHCID 22005300HCID 22005300, compound

Product 1

HCID 22004968HCID 22004968, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The intermediate obtained in Step B (200 mg, 0.40 mmol) was dissolved in anhydrous THF (5 mL), stirred under argon at room temperature and treated with 4-nitrothiophenol (118 mg, 0.6 mmol, 80% tech. grade) and N-methylmorpholine (0.2 mL, 1.8 mmol). The reaction mixture was allowed to stir at reflux for 18 hr, then cooled to room temperature. The mixture was treated with tetrabutylammonium fluoride (0.8 mL, 0.8 mmol, 1.0M in THF) and allowed to stir at room temperature for 24 hr. The solvent was removed in vacuo, the residue dissolved in ethyl acetate (100 mL), washed with 1N HCl (50 mL), sat. NaHCO3 (50 mL) and brine (50 mL), dried (MgSO4) and concentrated. Purification by chromatography through silica (step gradient 5-10% ethyl acetate/hexane) afforded the title compound as a lightly colored solid (130 mg, 0.28 mmol, 70%). 1H NMR (300 MHz, CDCl3): δ 8.08 (d, J=8.5 Hz, 2 H), 7.27 (m, 2 H), 7.13 (m, 4 H), 4.37 (d, J=5.5 Hz, 2 H), 3.91 (s, 2 H), 3.46 (sept, J=6.6 Hz, 1 H), 3.33 (sept, J=6.6 Hz, 1 H), 1.35 (d, J=6.6 Hz, 6 H), 1.34 (d, J=6.6 Hz, 6 H), 1.27 (t, J=5 Hz, 1 H). FAB-MS calcd for (C25H27FSN2O3) 454, found 455 (M+H). mp 178-180° C. Rf=0.3 (20% ethyl acetate/hexane).

Workup

  1. stirringto stir
  2. temperatureat reflux for 18 hr
  3. temperaturecooled to room temperature
  4. stirringto stir at room temperature for 24 hr
  5. customThe solvent was removed in vacuo
  6. dissolutionthe residue dissolved in ethyl acetate (100 mL)
  7. washwashed with 1N HCl (50 mL), sat. NaHCO3 (50 mL) and brine (50 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customPurification by chromatography through silica (step gradient 5-10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2f4f28f8a74343faaae667c8f343e144
Source dataset
uspto-grants-2001_04
Patent number
US06218431B1

Reaction notes

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