4-Methylmorpholine → HCID 24641315, compound

HRID 2381157Notes

Reaction equation

HRID 2381157 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][CH:14]([C:17](O)=[O:18])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.[F:38][C:39]([F:49])([F:48])[O:40][C:41]1[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=1>C(#N)C>[F:38][C:39]([F:48])([F:49])[O:40][C:41]1[CH:42]=[CH:43][C:44]([NH:45][C:17]([CH:14]2[CH2:13][CH2:12][N:11]([S:8]([C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=3)(=[O:9])=[O:10])[CH2:16][CH2:15]2)=[O:18])=[CH:46][CH:47]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 6008484-(Trifluoromethoxy)anilineHCID 7378401-(4-Methylbenzene-1-sulfonyl)piperidine-4-carboxylic acid

Product 1

HCID 24641315HCID 24641315, compoundYield 67.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-[(4-Methylphenyl)sulfonyl]-4-piperidinecarboxylic acid (0.283 g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) in acetonitrile (40 ml) were treated at RT and under an argon atmosphere with N-methyl-morpholine (0.2 g) and the mixture was stirred for 2 h at RT. 4-trifluoromethoxy-aniline (0.176 g) was then added and stirring was continued for 20 h at RT until completion of the reaction. The reaction mixture was partitioned between ethyl acetate and aqueous 1M HCl, the layers were separated and the organic layer washed with 2M aqueous KHCO3 then dried over Na2SO4. The solvent was evaporated off, the residue purified by flash chromatography (AcOEt/heptane, gradient from 0 to 30%) to give 1-(toluene-4-sulfonyl)-piperidine-4-carboxylic acid (4-trifluoromethoxy-phenyl)-amide (0.298 g) as a white solid. MS (ESI): 443.1 (MH+).

Workup

  1. stirringstirring
  2. customwas continued for 20 h at RT until completion of the reaction
  3. customThe reaction mixture was partitioned between ethyl acetate and aqueous 1M HCl
  4. customthe layers were separated
  5. washthe organic layer washed with 2M aqueous KHCO3
  6. dry with materialthen dried over Na2SO4
  7. customThe solvent was evaporated off
  8. customthe residue purified by flash chromatography (AcOEt/heptane, gradient from 0 to 30%)

Sources & evidence

ORD record
ord-c060cf795d52466cbbd1a628fface1e2
Source dataset
uspto-grants-2012_09
Patent number
US08258158B2

Reaction notes

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