Diisopropylethylamine → 2-(4-(4-Fluoro-benzoyl)-piperidin-1-ylmethyl]-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

HRID 362247Notes

Reaction equation

HRID 362247 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.C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:38][C:39]1[CH:52]=[CH:51][C:42]([C:43]([CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)=[O:44])=[CH:41][CH:40]=1.C(N(C(C)C)CC)(C)C.CCCCCC.C(OCC)(=O)C>CS(C)=O>[F:38][C:39]1[CH:40]=[CH:41][C:42]([C:43]([CH:45]2[CH2:50][CH2:49][N:48]([CH2:11][CH:12]3[O:25][C:16]4=[C:17]5[C:21](=[CH:22][CH:23]=[C:15]4[O:14][CH2:13]3)[NH:20][C:19](=[O:24])[CH2:18]5)[CH2:47][CH2:46]2)=[O:44])=[CH:51][CH:52]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 15381104(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-oneHCID 21226206Ethyl acetate hexaneHCID 73011315(4-Fluorophenyl)(piperidin-4-yl)methanone 4-methylbenzenesulfonate

Product 1

HCID 543705752-(4-(4-Fluoro-benzoyl)-piperidin-1-ylmethyl]-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-oneYield 40%

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), 4-(4-fluorobenzoyl)piperidine p-toluenesulfonate (4.68 g, 12.4 mmole) and diisopropylethylamine (2.15 ml, 12.3 mmole) were combined in 70 ml of dry DMSO and heated to 85° C. for 5 hours under a nitrogen atmosphere. The reaction was cooled and taken into 400 ml of 1:1 hexane/ethyl acetate. This was washed with 200 ml of water, with 200 ml of saturated brine, dried over MgSO4, filtered and concentrated to yield an oil. This oil was column chromatographed on silica gel using 0.75% methanol/CH2Cl2 as eluant to give the free base of the title compound as a yellow oil (0.40 g, 40%). This oil was crystallized from ethanol with the addition of a solution of fumaric acid in hot ethanol to give 0.37 g of the (S) enantiomer of the title compound as a light yellow solid fumarate, m.p. 237°-238° C.

Workup

  1. temperatureThe reaction was cooled
  2. washThis was washed with 200 ml of water, with 200 ml of saturated brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield an oil
  7. customchromatographed on silica gel using 0.75% methanol/CH2Cl2 as eluant

Sources & evidence

ORD record
ord-99ec1f92caa641a883d67e164a3c2b92
Source dataset
uspto-grants-1999_02
Patent number
US05869490

Reaction notes

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