Tetrahydrofuran → HCID 22643288, compound

HRID 2414846Notes

Reaction equation

HRID 2414846 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:26][O:25][C:16]3[CH:17]=[CH:18][C:19]4[N:20]=[C:21]([CH3:24])[O:22][C:23]=4[C:15]=3[O:14]2)(=O)=O)=CC=1.FC(F)(F)[C:29]1[CH:30]=[C:31]([C:35]2[CH2:36][CH2:37][NH:38][CH2:39][CH:40]=2)[CH:32]=[CH:33][CH:34]=1.C1COCC1.C(O)(=O)/C=C/C(O)=O>CN(C=O)C.C(O)C>[CH3:24][C:21]1[O:22][C:23]2=[C:15]3[C:16](=[CH:17][CH:18]=[C:19]2[N:20]=1)[O:25][CH2:26][CH:13]([CH2:12][N:38]1[CH2:37][CH:36]=[C:35]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:29][CH:30]=2)[CH2:40][CH2:39]1)[O:14]3

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 444972Fumaric AcidHCID 111280344-[3-(Trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridineHCID 11245807(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate

Product 1

HCID 22643288HCID 22643288, compoundYield 20.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate (0.40 g, 1.1 mmole) and 4-(3-trifluoromethyl-phenyl)-1,2,3,6-tetrahydro-pyridine (0.35 g, 1.54 mmole) were combined in 5 mL of DMF and 5 ml of THF under nitrogen. This solution was refluxed under nitrogen for overnight. After completion, the reaction was cooled to room temperature and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The resulting crude oil was column chromatographed on silica gel using first methylene chloride to remove impurities and then 1% methanol/methylene chloride to elute the (S)-enantiomer of the title compound. This was recrystallized from ethanol with the addition of one equivalent of fumaric acid to give 80 mg of white solid, m.p. 170-173° C.

Workup

  1. temperatureThis solution was refluxed under nitrogen for overnight
  2. custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  3. washThe organic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuum
  6. customchromatographed on silica gel using first methylene chloride
  7. customto remove impurities
  8. wash1% methanol/methylene chloride to elute the (S)-enantiomer of the title compound

Sources & evidence

ORD record
ord-8fecabd3a8fa4e1c8d246b92ebec0793
Source dataset
uspto-grants-2004_11
Patent number
US06815448B2

Reaction notes

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