Chloromethyl Methyl Ether → 1-Tetralone

HRID 1992864Notes

Reaction equation

HRID 1992864 reaction equation
[Br:1][C:2]1[C:11]([CH:12]([CH3:14])[CH3:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:15][CH3:16])[CH:8]=2)[C:3]=1[OH:17].C(N(C(C)C)CC)(C)C.[CH3:27][O:28][CH2:29]Cl>C1COCC1.C(Cl)Cl.O>[C:3]1(=[O:17])[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:10][CH2:11][CH2:2]1.[Br:1][C:2]1[C:11]([CH:12]([CH3:13])[CH3:14])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:15][CH3:16])[CH:8]=2)[C:3]=1[O:17][CH2:27][O:28][CH3:29]

Participants

8

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 68536740HCID 68536740, compound

Product 2

HCID 107241-TetraloneHCID 68537262HCID 68537262, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

2-Bromo-3-(1-methylethyl)-6-(methyloxy)-1-naphthalenol (69) (0.43 g, 1.45 mmol) was dissolved in THF (6 mL) followed by addition of diisopropylethylamine (1.02 mL, 5.78 mmol). Cooled in an ice bath, chloromethyl methyl ether (0.34 mL, 4.32 mmol) was added. The mixture was stirred at room temperature overnight. Diluted with CH2Cl2 (50 mL) and water (20 mL), and CH2Cl2 layer was separated. The aqueous layer was further extracted with CH2Cl2 (2×25 mL). The organic extracts were combined and washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a yellow oil. The crude product was purified by flash chromatography over SiO2 with hexanes:EtOAc (25:1) to give 0.43 g (79% from tetralone) of compound (70) as a light brown oil. 1H NMR (400 MHz, CDCl3): δ 1.32 (d, J=6.8 Hz, 6H), 3.49 (sept, J=6.8 Hz, 1H), 3.73 (s, 3H), 3.91 (s, 3H), 5.23 (s, 2H), 7.08 (d, J=2.4 Hz, 1H), 7.12 (dd, J1=9.1 Hz, J2=2.4 Hz, 1H), 7.43 (s, 1H), 8.02 (d, J=9.1 Hz, 1H).

Workup

  1. temperatureCooled in an ice bath
  2. customwas separated
  3. extractionThe aqueous layer was further extracted with CH2Cl2 (2×25 mL)
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customto give the crude product as a yellow oil
  9. customThe crude product was purified by flash chromatography over SiO2 with hexanes:EtOAc (25:1)

Sources & evidence

ORD record
ord-902343420ab748948820ac3cedb25926
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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