Methyl iodide → 3-Bromo-5,6,7,8-tetrahydronaphthalen-2-yl methyl ether

HRID 1063251Notes

Reaction equation

HRID 1063251 reaction equation
[Br:1][C:2]1[C:3]([OH:12])=[CH:4][C:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C:10]=2[CH:11]=1.[C:13]([O-])([O-])=O.[K+].[K+].IC>CN(C=O)C>[CH3:13][O:12][C:3]1[C:2]([Br:1])=[CH:11][C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 156376183-Bromo-5,6,7,8-tetrahydronaphthalen-2-ol

Product 1

HCID 222787363-Bromo-5,6,7,8-tetrahydronaphthalen-2-yl methyl etherYield 94.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A 21 mL oven dried scintillation vial with a Teflon lined cap was charged with 3-bromo-5,6,7,8-tetrahydronaphthalen-2-ol (568 mg, 2.50 mmol), powdered K2CO3 (691 mg, 5.00 mmol), dry DMF (7 mL) and iodomethane (0.622 mL, 10.00 mmol). The flask was purged with N2 sealed and heated on the orbital shaker to 50° C. for 4 hours. After cooling the reaction to ambient temperature, it was concentrated under high vacuum to remove DMF, and then partitioned between brine:water (1:1) and ethyl acetate (2×). The organics were combined, dried with Na2SO4, filtered and concentrated to a crude paste. The crude was purified by Biotage MPLC (90 g column, 2.5% ethyl acetate in heptane) to give 571 mg (94%) of 3-bromo-5,6,7,8-tetrahydronaphthalen-2-yl methyl ether as a white solid. Rf 0.57 (10% ethyl acetate in heptane) 1H NMR shows ˜6% contamination with the 1-bromo regio-iosmer. 1H NMR (400 MHz, CDCl3) δ 7.23 (s, 1 H), 6.59 (s, 1 H), 3.85 (s, 3 H), 2.69 (m, 4 H), 1.76 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 153.4, 137.4, 133.4, 130.8, 112.4, 108.3, 56.2, 29.5, 28.3, 23.1, 22.9.

Workup

  1. dry with materialA 21 mL oven dried scintillation vial with a Teflon
  2. customlined cap
  3. customThe flask was purged with N2
  4. customsealed
  5. temperatureAfter cooling
  6. customthe reaction to ambient temperature
  7. concentrationit was concentrated under high vacuum
  8. customto remove DMF
  9. custompartitioned between brine:water (1:1) and ethyl acetate (2×)
  10. dry with materialdried with Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated to a crude paste
  13. customThe crude was purified by Biotage MPLC (90 g column, 2.5% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-0e0d32dfc009451cbcd0ee9a0d3472ab
Source dataset
uspto-grants-2005_11
Patent number
US06964965B2

Reaction notes

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