2,3-Dihydroxybenzoic Acid → 4-Methoxybenzyl 2,3-Bis(4-methoxybenzyloxy)benzoate

HRID 2273673Notes

Reaction equation

HRID 2273673 reaction equation
[H-].[Na+].[OH:3][C:4]1[C:12]([OH:13])=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7].[CH3:14][O:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Br)=[CH:18][CH:17]=1>CN(C=O)C>[CH3:14][O:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20][O:3][C:4]2[C:12]([O:13][CH2:20][C:19]3[CH:22]=[CH:23][C:16]([O:15][CH3:14])=[CH:17][CH:18]=3)=[CH:11][CH:10]=[CH:9][C:5]=2[C:6]([O:8][CH2:20][C:19]2[CH:22]=[CH:23][C:16]([O:15][CH3:14])=[CH:17][CH:18]=2)=[O:7])=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 192,3-Dihydroxybenzoic AcidHCID 24758Sodium hydrideHCID 1650214-Methoxybenzyl bromide

Product 1

HCID 441575274-Methoxybenzyl 2,3-Bis(4-methoxybenzyloxy)benzoateYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60%, 4.69 g, 0.117 mol) was added in portions to 18 (5.47 g, 35.5 mmol) in DMF (150 mL) with ice bath cooling, and the mixture was stirred at 0° C. for 45 min and at room temperature for 1 h. A solution of 4-methoxybenzyl bromide (25.0 g, 0.124 mol) in DMF (50 mL) was added to the reaction mixture over 30 min. After stirring for 20 h, quenching with H2O (30 mL) at 0° C. was performed, and solvents were removed under high vacuum. The concentrate was dissolved in EtOAc (200 mL), which was washed with H2O (100 mL) and saturated NaCl (100 mL); solvent was removed in vacuo. Flash chromatography, eluting with 5:1 hexanes/EtOAc, gave 11.33 g (62%) of 19 as a white solid, mp 108° C.: 1H NMR δ 3.77 (s, 3H), 3.79 (s, 3H), 3.81 (s, 3H), 4.95 (s, 2H), 5.03 (s, 2H), 5.25 (s, 2H), 6.76 (d, 2H, J=8.8), 6.86 (d, 2H, J=8.8), 6.89 (d, 2H, J=8.4), 7.04 (t, 2H, J=7.8), 7.11 (dd, 2H, J=8.0, 2.0), 7.18 (d, 2H, J=8.8), 7.33-7.36 (m, 4H); 13C NMR δ 55.32, 55.37, 55.40, 66.81, 71.20, 75.31, 112.97, 113.61, 114.02, 118.16, 123.93, 127.08, 128.19, 128.75, 129.51, 129.73, 130.31, 130.41, 148.43, 152.95, 159.43, 159.62, 159.70, 166.44; HRMS m/z calcd for C31H30NaO7, 537.1889 (M+Na). found, 537.1884.

Workup

  1. temperaturecooling
  2. stirringAfter stirring for 20 h
  3. customquenching with H2O (30 mL) at 0° C.
  4. customsolvents were removed under high vacuum
  5. dissolutionThe concentrate was dissolved in EtOAc (200 mL)
  6. washwhich was washed with H2O (100 mL) and saturated NaCl (100 mL)
  7. customsolvent was removed in vacuo
  8. washFlash chromatography, eluting with 5:1 hexanes/EtOAc

Sources & evidence

ORD record
ord-bbdf0cee328240cfbf75616415dd82be
Source dataset
uspto-grants-2015_09
Patent number
US09125950B2

Reaction notes

Loading…