Thiomorpholine → 2-[(1S)-6-(4-Thiomorpholinyl)-3,4-dihydro-1H-2-benzopyran-1-yl]ethanol

HRID 2056778Notes

Reaction equation

HRID 2056778 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C@H:10]([CH2:11][CH2:12][OH:13])[O:9][CH2:8][CH2:7][C:6]=2[CH:14]=1.[NH:15]1[CH2:20][CH2:19][S:18][CH2:17][CH2:16]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:15]1([C:2]2[CH:3]=[CH:4][C:5]3[C@H:10]([CH2:11][CH2:12][OH:13])[O:9][CH2:8][CH2:7][C:6]=3[CH:14]=2)[CH2:20][CH2:19][S:18][CH2:17][CH2:16]1

Participants

8

Reactant 4

HCID 67164ThiomorpholineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 536878432-((1S)-6-Bromo-3,4-dihydro-1H-2-benzopyran-1-yl)ethanol

Product 1

HCID 693083652-[(1S)-6-(4-Thiomorpholinyl)-3,4-dihydro-1H-2-benzopyran-1-yl]ethanol

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

2-((1S)-6-Bromo-3,4-dihydro-1H-2-benzopyran-1-yl)ethanol (0.26 g, 0.99 mmol) was dissolved in dry toluene (10 mL) and degassed. Thiomorpholine (0.14 mL, 1.48 mmol), tris(dibenzylideneacetone)dipalladium (51 mg), (+/−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (77 mg) and sodium tert-butoxide (0.126 g, 1.3 mmol) were added and the mixture heated under reflux with stirring, under a nitrogen atmosphere, for 24 h. The reaction was cooled to room temperature, diluted with dichloromethane, filtered through celite and washed with water. The organic extracts were dried (MgSO4), filtered and evaporated in vacuo. The crude product was purified by flash chromatography on silica, to yield the title compound.

Workup

  1. customdegassed
  2. temperaturethe mixture heated
  3. temperatureunder reflux
  4. filtrationfiltered through celite
  5. washwashed with water
  6. dry with materialThe organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude product was purified by flash chromatography on silica

Sources & evidence

ORD record
ord-76afd44a0f904b60a5419ac3aac33177
Source dataset
uspto-grants-2008_02
Patent number
US07335660B2

Reaction notes

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