Morpholine → HCID 178420446, compound

HRID 1241512Notes

Reaction equation

HRID 1241512 reaction equation
[N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([C@@H:13]3[CH2:16][C@H:15]([CH2:17]OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:14]3)=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1>CC(N(C)C)=O>[N:1]1([CH2:6][C:7]2[CH:8]=[CH:9][C:10]([C@@H:13]3[CH2:14][C@H:15]([CH2:17][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[CH2:16]3)=[CH:11][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 178427759HCID 178427759, compound

Product 1

HCID 178420446HCID 178420446, compoundYield 68.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirring cis-toluene-4-sulfonic acid 3-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethyl ester (example 47) (0.41 g, 1.0 mmol) in DMA (5 mL) was added an amine for example morpholine (0.18 g, 2 mmo). The reaction was then heated to 100° C. (oil bath). After 4 hr the reaction was cooled to rt and concentrated under reduced pressure. Purification of this material was accomplished by flash column chromatography, using a 45 g ISCO column, eluting with a gradient of 5%, 10%, 20%, 60% MeOH/CH2Cl2 with 0.1% NH4OH. The product containing fractions were collected and concentrated to yield the title compound (214 mg) as the TsOH salt. This material was free based by stirring in solid K2CO3 and MeOH for 2 hours. After 2 hr the methanolic solution was concentrated, diluted with CH2Cl2, filtered, and concentrated under reduced pressure to give the free base. The HCl salt was made by taken the freebase up in EtOAc and then adding a solution of HCl (2 eq, 1 M HCl, THF) to give a colorless solid.

Workup

  1. temperatureAfter 4 hr the reaction was cooled to rt
  2. concentrationconcentrated under reduced pressure
  3. customPurification of this material
  4. washeluting with a gradient of 5%, 10%, 20%, 60% MeOH/CH2Cl2 with 0.1% NH4OH
  5. additionThe product containing fractions
  6. customwere collected
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3c6cccffff734aadad48e5286b37a7a5
Source dataset
uspto-grants-2006_10
Patent number
US07115600B2

Reaction notes

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