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

HRID 1737414Notes

Reaction equation

HRID 1737414 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.[F:27][C:28]([F:38])([F:37])[C:29]1[CH:36]=[CH:35][C:32]([CH2:33][NH2:34])=[CH:31][CH:30]=1.O>CS(C)=O>[F:27][C:28]([F:37])([F:38])[C:29]1[CH:36]=[CH:35][C:32]([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)=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 962WaterHCID 768044-(Trifluoromethyl)benzylamineHCID 15381104(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

Product 1

HCID 99769152-(4-Trifluoromethyl-benzylamino-methyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-oneYield 54%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
85 °C

Procedure

(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one (1.03 g, 2.75 mmole) and 4-trifluoromethylbenzylamine (1.60 ml, 11.2 mmole) were combined in 15 ml of dry DMSO and heated to 85° C. for 3.5 hours under a nitrogen atmosphere. After cooling to room temperature, 150 ml of water was added and the mixture was extracted twice with 250 ml portions of 35% ethyl acetate in hexane. The combined organic phases were washed with brine, dried over MgSO4, filtered and concentrated in vacuum to yield an oil, which was column chromatographed on silica gel using 5% methanol/CH2Cl2 as eluant. The free base of the title compound (0.56 g, 54%) thus obtained was crystallized from ethanol with the addition of one equivalent of fumaric acid to give 0.06 g of the (S) enantiomer of the title compound as an off-white solid fumarate, m.p. 211-212° C.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture was extracted twice with 250 ml portions of 35% ethyl acetate in hexane
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum
  7. customto yield an oil, which
  8. customchromatographed on silica gel using 5% methanol/CH2Cl2 as eluant

Sources & evidence

ORD record
ord-7fc53eaa314143fdb5a6496e4a15b932
Source dataset
uspto-grants-1999_10
Patent number
US05962465

Reaction notes

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