Cyclohexanemethylamine → 2-(Cyclohexylmethylamino-methyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

HRID 1292196Notes

Reaction equation

HRID 1292196 reaction equation
C1(C)C=CC(S(O[CH2:11][C@@H:12]2[O:25][C:16]3=[C:17]4[C:21](=[CH:22][CH:23]=[C:15]3[O:14][CH2:13]2)[NH:20][C:19](=[O:24])[CH2:18]4)(=O)=O)=CC=1.[CH:27]1([CH2:33][NH2:34])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.C(O)(=O)/C=C/C(O)=O>CS(C)=O.C(O)(C)C>[CH:27]1([CH2:33][NH:34][CH2:11][CH:12]2[O:25][C:16]3=[C:17]4[C:21](=[CH:22][CH:23]=[C:15]3[O:14][CH2:13]2)[NH:20][C:19](=[O:24])[CH2:18]4)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

6

Reactant 3

HCID 76688CyclohexanemethylamineHCID 444972Fumaric AcidHCID 15381104(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

Product 1

HCID 696197422-(Cyclohexylmethylamino-methyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3776IsopropanolSolvent2×

Conditions

Temperature
80 °C

Procedure

(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one (0.80 g, 2.13 mmole), and cyclohexylmethylamine (1.33 g, 11.7 mmole) were combined in 15 ml of dry DMSO and heated to 80° C. for 6 hours under a nitrogen atmosphere. The reaction was allowed to cool and was partitioned between 100 ml of ethyl acetate and 150 ml of deionized water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated to yield a black oil. This oil was column chromatographed on silica gel using 0.75% methanol/CH2Cl2 to remove impurities. A concentration of 2% methanol/CH2Cl2 eluted the desired product, which was as an oil (0.38 g, 56%) upon concentration in vacuum. This oil was crystallized from isopropanol with the addition of a solution of fumaric acid (0.15 g, 1.3 mmole) in hot isopropanol to give 0.39 g of the (S) enantiomer of the title compound as an off-white solid monofumarate, half hydrate, m.p. 187°-188° C.

Workup

  1. temperatureto cool
  2. customwas partitioned between 100 ml of ethyl acetate and 150 ml of deionized water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a black oil
  8. customchromatographed on silica gel using 0.75% methanol/CH2Cl2
  9. customto remove impurities
  10. washA concentration of 2% methanol/CH2Cl2 eluted the desired product, which
  11. concentrationwas as an oil (0.38 g, 56%) upon concentration in vacuum

Sources & evidence

ORD record
ord-37935032645343e985e588684a9f9b8b
Source dataset
uspto-grants-1998_05
Patent number
US05756532

Reaction notes

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