Lithium Hydroxide → HCID 59199322, compound

HRID 2089488Notes

Reaction equation

HRID 2089488 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([I:9])[CH:4]=1.C[O:11][C:12](=O)[CH2:13][SH:14].C([O-])([O-])=O.[K+].[K+].[OH-].[Li+].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>CC(C)=O.ClC1C=CC=CC=1.C(O)(=O)C.O.CO>[I:9][C:5]1[CH:4]=[C:3]2[C:8]([C:12](=[O:11])[CH2:13][S:14][CH2:2]2)=[CH:7][CH:6]=1

Participants

11

Reactant 5

HCID 3939Lithium HydroxideHCID 11430Potassium CarbonateHCID 14812Phosphorus oxide (P4O10)HCID 16907Methyl ThioglycolateHCID 27593613-Iodobenzyl bromide

Product 1

HCID 59199322HCID 59199322, compound

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 180AcetoneSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 7964ChlorobenzeneSolvent

Procedure

To a solution of 1-bromomethyl-3-iodo-benzene (CAS#49617-83-6, 25.0 g, 84 mmol) in acetone (500 mL) is added mercapto-acetic acid methyl ester (9.0 g, 85 mmol) followed by K2CO3 (15.2 g 110 mmol). The reaction is permitted to stir overnight. The next morning the reaction is filtered and concentrated. The resulting residue containing (3-iodo-benzylsulfanyl)-acetic acid methyl ester is then dissolved in methanol (300 mL). The methanol solution is charged with water (100 mL) and lithium hydroxide (6.0 g, 252 mmol). The reaction is permitted to stir at room temperature until the starting ester is consumed as determined by TLC analysis. The reaction is then brought to a pH<4 by the addition of 3N aqueous HCl. The reaction is then concentrated to approximately ¾ of its original volume and diluted with ethyl acetate. The layers are separated and the organic layer is dried with Na2SO4, filtered and concentrated to afford a residue containing 3-iodo-benzylsulfanyl)-acetic acid. The residue is dissolved in chlorobenzene (500 mL) and treated with P2O5 (64 g, 450 mmol). The reaction is heated at reflux overnight. The reaction is then cooled to room temperature and filtered. The eluent is then concentrated to dryness. The resulting residue is dissolved in ethyl acetate and washed with brine. The organic layer is then dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-hexanes, 0:1 to 1:5) to afford 7-iodo-isothiochroman-4-one; MS: (ESI) m/z 308.0 (M+NH4)+

Workup

  1. filtrationThe next morning the reaction is filtered
  2. concentrationconcentrated
  3. additionThe resulting residue containing (3-iodo-benzylsulfanyl)-acetic acid methyl ester
  4. dissolutionis then dissolved in methanol (300 mL)
  5. customis consumed
  6. additionThe reaction is then brought to a pH<4 by the addition of 3N aqueous HCl
  7. concentrationThe reaction is then concentrated to approximately ¾ of its original volume
  8. additiondiluted with ethyl acetate
  9. customThe layers are separated
  10. dry with materialthe organic layer is dried with Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto afford a residue
  14. temperatureThe reaction is heated
  15. temperatureat reflux overnight
  16. filtrationfiltered
  17. concentrationThe eluent is then concentrated to dryness
  18. dissolutionThe resulting residue is dissolved in ethyl acetate
  19. washwashed with brine
  20. dry with materialThe organic layer is then dried with Na2SO4
  21. filtrationfiltered
  22. concentrationconcentrated
  23. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-hexanes, 0:1 to 1:5)

Sources & evidence

ORD record
ord-c7a266866c0546558728f993ae6d8965
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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