Monobenzone → Methyl 2-[(4-{2-[4-(benzyloxy)phenoxy]ethyl}phenoxy)methyl]benzoate

HRID 2112002Notes

Reaction equation

HRID 2112002 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[CH:21]=[CH:20][C:7]([O:8][CH2:9][C:10]2[CH:19]=[CH:18][CH:17]=[CH:16][C:11]=2[C:12]([O:14][CH3:15])=[O:13])=[CH:6][CH:5]=1.[CH2:22]([O:29][C:30]1[CH:35]=[CH:34][C:33](O)=[CH:32][CH:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[CH2:22]([O:29][C:30]1[CH:35]=[CH:34][C:33]([O:1][CH2:2][CH2:3][C:4]2[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]3[CH:19]=[CH:18][CH:17]=[CH:16][C:11]=3[C:12]([O:14][CH3:15])=[O:13])=[CH:20][CH:21]=2)=[CH:32][CH:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 7638MonobenzoneHCID 11776TriphenylphosphineHCID 58820416Methyl 2-{[4-(2-hydroxyethyl)phenoxy]methyl}benzoate

Product 1

HCID 68870647Methyl 2-[(4-{2-[4-(benzyloxy)phenoxy]ethyl}phenoxy)methyl]benzoateYield 42.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
55 °C

Procedure

Methyl 2-{[4-(2-hydroxyethyl)phenoxy]methyl}benzoate (1 g, 3.49 mmol), 4-(benzyloxy)phenol (0.7 g, 3.49 mmol) and triphenylphosphine (1.01 g, 3.84 mmol) was added to a dry round bottomed flask fitted with a septum. N2 was flushed through the flask for 5 minutes followed by the addition of dry toluene (30 ml) and diisopropylazo-dicarboxylate (0.78 g, 3.84 mmol). The reaction mixture was stirred at 55° C. overnight. The solvent was removed by evaporation and the crude material was purified by preparative HPLC (started with acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4). After removing the solvent by evaporation, 0.7 g of methyl 2-[(4-{2-[4-(benzyloxy)phenoxy]ethyl}phenoxy)methyl]benzoate was isolated (yield 42.8%).

Workup

  1. customfitted with a septum
  2. customN2 was flushed through the flask for 5 minutes
  3. customThe solvent was removed by evaporation
  4. customthe crude material was purified by preparative HPLC (
  5. concentrationthe acetonitrile concentration
  6. temperaturewas increased to 100%
  7. additiona mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min)
  8. additionThe product containing fractions
  9. customthe acetonitrile was removed by evaporation
  10. additionEtOAc (10 ml) was added
  11. washthe organic phase was washed with two portions of brine
  12. dry with materialdried (MgSO4)
  13. customAfter removing the solvent
  14. customby evaporation

Sources & evidence

ORD record
ord-19468a65a0584f9e857d43ee1fed052c
Source dataset
uspto-grants-2009_04
Patent number
US07521461B2

Reaction notes

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