Bromine → 2-Bromo-3-methyl-6-(methylsulfonyl)naphthalen-1-ol

HRID 926139Notes

Reaction equation

HRID 926139 reaction equation
[CH3:1][CH:2]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([S:12]([CH3:15])(=[O:14])=[O:13])[CH:9]=2)[C:4](=[O:16])[CH2:3]1.[Br:17]Br>ClCCl>[Br:17][C:3]1[C:2]([CH3:1])=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([S:12]([CH3:15])(=[O:14])=[O:13])[CH:9]=2)[C:4]=1[OH:16]

Participants

4

Reactant 2

HCID 24408Bromine2×HCID 896767373-methyl-6-(methylsulfonyl)-3,4-dihydronaphthalen-1(2H)-one

Product 1

HCID 896769962-Bromo-3-methyl-6-(methylsulfonyl)naphthalen-1-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-methyl-6-(methylsulfonyl)-3,4-dihydronaphthalen-1(2H)-one (7.64 g, 32.06 mmol) in dichloromethane (200 mL) at room temperature was added a solution of bromine (3.38 mL, 65.72 mmol) in dichloromethane (5 mL) over 30 minutes to give an orange mixture. The reaction mixture was stirred at room temperature for 2 hours, then more bromine (0.3 mL) was added and stirring continued for 1 hour. The reaction mixture was concentrated and co-evaporated with dichloromethane and dried under house vacuum. The resulting off-white residue was suspended in acetonitrile and cooled to −40° C. 1,8-Diazabicyclo[5.4.0]dunde-7-ene (7.19 mL, 48.09 mmol) was added over 5 minutes and the reaction mixture was warmed to room temperature overnight. The reaction mixture was concentrated, diluted with ethyl acetate, washed with dilute acetic acid solution, brine and dried (MgSO4) and filtered. Concentration and purification by flash column chromatography (silica gel, 20-60% ethyl acetate/hexanes) gave an impure product. Repurification by flash column chromatography (silica gel, 40% ethyl acetate/hexanes) gave the desired product. LCMS-ESI+ (m/z): [M−H]− calcd for C12H10BrO3S: 314.2. Found: 313.2, 315.1.

Workup

  1. customto give an orange mixture
  2. stirringstirring
  3. waitcontinued for 1 hour
  4. concentrationThe reaction mixture was concentrated and co-evaporated with dichloromethane
  5. customdried under house vacuum
  6. temperaturecooled to −40° C
  7. addition1,8-Diazabicyclo[5.4.0]dunde-7-ene (7.19 mL, 48.09 mmol) was added over 5 minutes
  8. temperaturethe reaction mixture was warmed to room temperature overnight
  9. concentrationThe reaction mixture was concentrated
  10. additiondiluted with ethyl acetate
  11. washwashed with dilute acetic acid solution, brine
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationConcentration and purification by flash column chromatography (silica gel, 20-60% ethyl acetate/hexanes)
  15. customgave an impure product
  16. customRepurification by flash column chromatography (silica gel, 40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-434a828b68a047ad8c8c6d6c66e94356
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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