Water → Ethyl 3-chloro-8-hydroxynaphthalene-2-carboxylate

HRID 1968759Notes

Reaction equation

HRID 1968759 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15]([Cl:16])=[CH:14][C:13]2[C:8](=[C:9]([O:17]C)[CH:10]=[CH:11][CH:12]=2)[CH:7]=1)=[O:5])[CH3:2].B(Cl)(Cl)Cl.O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[C:15]([Cl:16])=[CH:14][C:13]2[C:8](=[C:9]([OH:17])[CH:10]=[CH:11][CH:12]=2)[CH:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 962WaterHCID 25135Boron TrichlorideHCID 66882254Ethyl 3-chloro-8-methoxynaphthalene-2-carboxylate

Product 1

HCID 66881802Ethyl 3-chloro-8-hydroxynaphthalene-2-carboxylate

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Tetrabutylammonium iodide (3.74 g, 10.12 mmol, 1.3 equiv) was added to a solution of 3-chloro-8-methoxy-naphthalene-2-carboxylic acid ethyl ester (2.06 g, 7.79 mmol) in anhydrous CH2Cl2 (39 ml). After cooling to −78° C., BCl3 (1M solution in CH2Cl2, 19.46 ml, 19.46 mmol, 2.5 equiv) was added dropwise. The reaction mixture was stirred at −78° C. for 30 minutes and then let warm to room temperature. After 2 hours at room temperature, cold water (4° C., 40 ml) was added slowly, and the resulting mixture was vigorously stirred for 30 minutes before it was extracted with EtOAc (800 ml total). The combined organic layers were washed with concentrated aqueous NaHCO3 solution (100 ml) and concentrated aqueous NH4Cl solution (100 ml), dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (gradient of hexane/EtOAc 100:0 to 6:4) afforded the title compound (1.84 g, 95%, inseparable 1:1.3 mixture of regioisomers A:B) as a slightly yellow solid. 1H NMR (400 MHz, d6-DMSO): δ=10.69 (br s, 1H isomer B), 10.55 (br s, 1H isomer A), 8.60 (s, 1H isomer B), 8.35 (s, 1H isomer A), 8.16 (s, 1H isomer A), 8.06 (s, 1H isomer B), 7.55-7.36 (m, 2H isomer A+2H isomer B), 7.01 (d, J=7.6 Hz, 1H isomer A), 6.95 (d, J=7.5 Hz, 1H isomer B), 4.36 (q, J=7.1 Hz, 2H isomer A+2H isomer B), 1.37-1.33 (m, 3H isomer A+3H isomer B). MS (ES+): 251 (M+H)+.

Workup

  1. temperaturelet warm to room temperature
  2. waitAfter 2 hours at room temperature
  3. stirringthe resulting mixture was vigorously stirred for 30 minutes before it
  4. extractionwas extracted with EtOAc (800 ml total)
  5. washThe combined organic layers were washed with concentrated aqueous NaHCO3 solution (100 ml) and concentrated aqueous NH4Cl solution (100 ml)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification via flash chromatography (gradient of hexane/EtOAc 100:0 to 6:4)

Sources & evidence

ORD record
ord-71d4be60f67d4197b27cc30517dee040
Source dataset
uspto-grants-2013_04
Patent number
US08426440B2

Reaction notes

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