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Sulfur Dioxide → 3-Benzyloxy-4-chlorosulfonyl-benzoic acid methyl ester

HRID 1814356
Notes
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Reaction equation

HRID 1814356 reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][C:7](N)=[C:6]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:5]=1.B(F)(F)F.CCOCC.N(OC(C)(C)C)=O.[Cl-:36].[Li+].[S:38](=[O:40])=[O:39].COC(=O)C1C=CC(N=N)=C(OCC2C=CC=CC=2)C=1>[Cu]Cl.C(OCC)(=O)C.C(O)(=O)C.O1CCOCC1.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][C:7]([S:38]([Cl:36])(=[O:40])=[O:39])=[C:6]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:5]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

12

Reactant 6

HCID 1119Sulfur DioxideHCID 8000Boron trifluoride etherateHCID 10906Tert-Butyl nitriteHCID 433294Lithium ChlorideHCID 25052945Methyl 4-amino-3-(benzyloxy)benzenecarboxylateHCID 696930003-Benzyloxy-4-diazenyl-benzoic acid methyl ester

Product 1

HCID 86588224
3-Benzyloxy-4-chlorosulfonyl-benzoic acid methyl ester

Reagents, catalysts & solvents 5

HCID 62652Cuprous chlorideCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
-10 °C

Procedure

REFERENCE: J. Org. Chem, 1979, 44, 1572-1574. To a −10° C. (acetone/ice/sodium chloride) methylene chloride solution of 4-amino-3-benzyloxy-benzoic acid methyl ester (8.7 g, 33.8 mmol) was added boron trifluoride diethyl etherate (12.4 mL, 101.5 mmol) dropwise. A methylene chloride solution (5.2 mL) of tert-butyl nitrite (4.8 mL, 40.5 mmol) was then slowly added dropwise. The reaction was allowed to stir at −10° C. for approximately 30 min. At this point a small aliquot (2 mL) was removed and concentrated under reduced pressure. 1H NMR showed that the reaction was complete. Chilled pentane (125 mL) was then added to precipitate the diazo-salt from the methylene chloride. The 3-benzyloxy-4-diazenyl-benzoic acid methyl ester was then dissolved in dioxane (˜150 mL) and acetonitrile (˜50 mL) and used without any further manipulation. To a −10° C. (acetone/ice/sodium chloride) solution of dioxane (150 mL) and acetic acid (150 mL) was added copper (I) chloride (0.99 g, 10.5 mmol) and lithium chloride (8.5 g, 201 mmol). Sulfur dioxide (˜150 mL) was then condensed into this solution using a −78° C. cold finger. The above solution of 3-benzyloxy-4-diazenyl-benzoic acid methyl ester was then poured into this solution. The reaction was kept at 0° C. for 4-5 h and then placed into a preheated oil bath at 65° C. overnight. The reaction was then cooled and poured into ethyl acetate (600 mL) and washed in succession with water and 1N sodium hydroxide. A final wash with saturated aqueous sodium chloride was done and the organic layer was then dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 3-benzyloxy-4-chlorosulfonyl-benzoic acid methyl ester as a foam. This was used in the next step without further purification. The product moved on TLC to a Rf of 0.5 in 30% ethyl acetate/hexane. 1H NMR (CDCl3) 8.00(d,1H), 7.75(s,1H), 7.67(d,1H), 7.49(d,2H), 7.35(m,3H), 5.35(s,2H), 3.91(s,3H).

Workup

  1. customAt this point a small aliquot (2 mL) was removed
  2. concentrationconcentrated under reduced pressure
  3. additionChilled pentane (125 mL) was then added
  4. customto precipitate the diazo-salt from the methylene chloride
  5. dissolutionThe 3-benzyloxy-4-diazenyl-benzoic acid methyl ester was then dissolved in dioxane (˜150 mL)
  6. customcondensed into this solution
  7. customusing a −78° C.
  8. waitThe reaction was kept at 0° C. for 4-5 h
  9. waitplaced into a preheated oil bath at 65° C. overnight
  10. temperatureThe reaction was then cooled
  11. washwashed in succession with water and 1N sodium hydroxide
  12. washA final wash with saturated aqueous sodium chloride
  13. dry with materialthe organic layer was then dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ec95be34cccd43c38c89d437179f9b5c
Source dataset
uspto-grants-2005_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06875765B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes