Chloromethyl Methyl Ether → 2-Bromo-6-methoxy-1-methoxymethoxy-3-propyl-naphthalene

HRID 1992977Notes

Reaction equation

HRID 1992977 reaction equation
[Br:1][C:2]1[C:11]([CH2:12][CH2:13][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[OH:17].C(N(C(C)C)CC)(C)C.[CH3:27][O:28][CH2:29]Cl>C1COCC1.O>[Br:1][C:2]1[C:11]([CH2:12][CH2:13][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

6

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 68537594HCID 68537594, compound

Product 1

HCID 685347832-Bromo-6-methoxy-1-methoxymethoxy-3-propyl-naphthaleneYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-Bromo-6-methoxy-3-propyl-naphthalen-1-ol (94) (1.41 g, 4.78 mmol) in dry THF (23 mL) at 0° C. was added diisopropylethylamine (3.3 mL, 19.1 mmol) followed by chloromethyl methyl ether (1.1 mL, 14.3 mmol) slowly. Reaction mixture was stirred at ambient temperature for 24 h. Reaction mixture was diluted with water and the aqueous layer was extracted with DCM, washed organic layer with brine, dried over Na2SO4, filtered and concentrated. The crude material was purified using 1:9 EtOAc:hexanes to provide 1.26 g (78%) of the title compound (95) as a solid. 1H NMR (400 MHz, d-CDCl3): δ 1.01 (t, J=7.4 Hz, 3H), 1.70-1.75 (m, 2H), 2.85 (t, J=7.7 Hz, 2H), 3.72 (s, 3H), 3.91 (s, 3H), 5.23 (s, 2H), 7.04 (s, 1H), 7.12 (dd, J1=2.6 Hz, J2=9.1 Hz, 1H), 7.39 (s, 1H), 8.03 (d, J=9.1 Hz, 1H).

Workup

  1. customReaction mixture
  2. customReaction mixture
  3. extractionthe aqueous layer was extracted with DCM
  4. washwashed organic layer with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified

Sources & evidence

ORD record
ord-e575497b563e4fa8a9249e48e386d741
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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