Sulfur Dioxide → HCID 22504018, compound

HRID 1814325Notes

Reaction equation

HRID 1814325 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](N)=[C:4]([O:9][CH2:10][CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=2)[CH:3]=1.B(F)(F)F.CCOCC.N(OC(C)(C)C)=O.[Li+].[Cl-:39].[S:40](=[O:42])=[O:41]>[Cu]Cl.CCOC(C)=O.C(O)(=O)C.O1CCOCC1.CCCCC.C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:40]([Cl:39])(=[O:42])=[O:41])=[C:4]([O:9][CH2:10][CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=2)[CH:3]=1

Participants

12

Reactant 5

HCID 1119Sulfur DioxideHCID 8000Boron trifluoride etherateHCID 10906Tert-Butyl nitriteHCID 433294Lithium ChlorideHCID 22504195HCID 22504195, compound

Product 1

HCID 22504018HCID 22504018, compound

Reagents, catalysts & solvents 6

HCID 62652Cuprous chlorideCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8003PentaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
-10 °C

Procedure

To a −10° C. (acetone/ice/sodium chloride) CH2Cl2 solution of 4-fluoro-2-(2-naphthalen-1-yl-ethoxy)-phenylamine (15.0 g, 53.30 mmol) was added boron trifluoride diethyl etherate (19.7 mL, 160.0 mmol) dropwise. Tert-Butyl nitrite (8.30 mL, 69.3 mmol) was then slowly added dropwise. The reaction mixture was allowed to stirred at −10° C. for 30 min. Chilled pentane (150 mL) was then added to precipitate the diazo-salt from CH2Cl2. The diazo-salt was then dissolved in dioxane:acetonitrile (3:1, 150 mL) kept at 0° C. In a three-necked flask to a solution of dioxane (150 mL) and acetic acid (150 mL) at −10° C. was added copper (I) chloride (1.60 g, 16.0 mmol) and LiCl (33.0 g, 319 mmol). Sulfur dioxide (˜100 mL) was then condensed into this solution using a −78° C. cold finger. The above diazo-salt solution was then poured into this solution. The reaction was kept at 0° C. for 2 h and then placed into a preheated oil bath at 65° C. for 12 h. The reaction was then cooled and poured into EtOAc (500 mL) and washed with water, and 1 N sodium hydroxide. The organic layer was then dried (MgSO4), filtered and concentrated under reduced pressure to yield 4-fluoro-2-(2-naphthalen-1-yl-ethoxy)-benzenesulfonyl chloride as a yellowish foam (19.90 g, 98%). 1H NMR (CDCl3, 400 MHz) 8.05 (d, 1H), 7.90 (d, 1H), 7.87 (d, 1H), 7.78 (d, 1H), 7.60-6.42 (m, 4H), 6.78-6.64 (m, 2H), 4.21 (t, 2H), 3.79 (t, 2H).

Workup

  1. customto precipitate the diazo-salt from CH2Cl2
  2. dissolutionThe diazo-salt was then dissolved in dioxane:acetonitrile (3:1, 150 mL)
  3. customkept at 0° C
  4. customcondensed into this solution
  5. customusing a −78° C.
  6. waitThe reaction was kept at 0° C. for 2 h
  7. waitplaced into a preheated oil bath at 65° C. for 12 h
  8. temperatureThe reaction was then cooled
  9. washwashed with water, and 1 N sodium hydroxide
  10. dry with materialThe organic layer was then dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ddae6d209b314af6b13489c92d165149
Source dataset
uspto-grants-2005_04
Patent number
US06875765B2

Reaction notes

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