Tetrahydrofuran → 1-Naphthol

HRID 1077574Notes

Reaction equation

HRID 1077574 reaction equation
[Li][CH2:2][CH2:3][CH2:4][CH3:5].C(N(CC)[C:9](=[O:14])[CH:10]=[C:11]([CH3:13])C)C.[CH2:17]1COC[CH2:18]1>C(NC1CCCCC1)(C)C>[CH:3]1[CH:4]=[CH:5][C:17]2[C:18](=[CH:13][CH:11]=[CH:10][C:9]=2[OH:14])[CH:2]=1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 223380N,N-Diethyl-3-methyl-2-butenamideHCID 178418339Butyllithium

Product 1

HCID 70051-NaphtholYield 29%

Reagents, catalysts & solvents 1

HCID 62386CyclohexylisopropylamineCatalyst

Conditions

Temperature
0 °C

Procedure

To a stirred solution of isopropylcyclohexylamine (7.5 mL, 0.45 mmol) in 60 mL of THF at -78° C. under N2 was added n-BuLi (20.0 mL, 50.0 mmol, 2.5M in hexanes). The mixture was stirred for 20 min, warmed to 0° C., and then stirred for 1 h. The mixture was cooled to -78° C. and solution of N,N-diethyl-3,3-dimethylacrylamide (2.10 g, 13.0 mmol) in 40 mL of THF was added. This mixture was stirred at -78° C. for 1 h. The cold bath was removed and the reaction mixture was allowed to warm to -20° C. over a period of 10 min. A solution of 2,4-dibromo-1-methoxymethoxybenzene (9) in 30 mL of THF was added. The reaction mixture was stirred overnight at room temperature, and then quenched with saturated NH4Cl Et2O was added and the solution was washed with H2O, brine, dried over Na2SO4, and concentrated in vacuo. The crude product was purified by flash chromatography (hexanes/EtOAc; 9:1) to yield napthol 12 (1.15 g, 29%) as a brown oil; 1H NMR (CDCl3, 300 MHz): δ9.31 [s, OH], 7.54 [d, J=8.4 Hz, ArH(6)], 7.49 [s, ArH(4)], 6.82 [s, ArH(2)[, 6.81 [d, J=8.4 Hz, ArH(7)], 5.46 [s, OCH2OCH3 ], 3.55 [s, OCH3 ], and 2.47 [s, ARCH3 (3)]; 13C NMR (CDCl3, 75 MHz): 67 154.3, 153.5, 139.5, 134.5, 129.6, 118.2, 115.5, 114.5, 113.6, 107.3, 95.9, 56.9, and 22.0; LRMS (EI): m/z 298 (M+, 13), 296 (M+, 11), 128 (5), 115 (9), and 45 (100).

Workup

  1. stirringstirred for 1 h
  2. temperatureThe mixture was cooled to -78° C.
  3. stirringThis mixture was stirred at -78° C. for 1 h
  4. customThe cold bath was removed
  5. temperatureto warm to -20° C. over a period of 10 min
  6. additionA solution of 2,4-dibromo-1-methoxymethoxybenzene (9) in 30 mL of THF was added
  7. stirringThe reaction mixture was stirred overnight at room temperature
  8. customquenched with saturated NH4Cl Et2O
  9. additionwas added
  10. washthe solution was washed with H2O, brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated in vacuo
  13. customThe crude product was purified by flash chromatography (hexanes/EtOAc; 9:1)

Sources & evidence

ORD record
ord-d92016688ac440c09840b2c2b0e498b9
Source dataset
uspto-grants-1996_08
Patent number
US05543523

Reaction notes

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