Boron tribromide → ({4-[(6-Hydroxy-3-methyl-2-phenyl-1-naphthalenyl)oxy]phenyl}oxy)acetic acid

HRID 1992983Notes

Reaction equation

HRID 1992983 reaction equation
[CH3:1][C:2]1[C:3]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:4]([O:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]([OH:25])=[O:24])=[CH:17][CH:16]=2)[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12]C)=[CH:7][CH:6]=2.B(Br)(Br)Br.C([O-])(O)=O.[Na+]>C(Cl)Cl>[OH:12][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[C:4]([O:14][C:15]1[CH:16]=[CH:17][C:18]([O:21][CH2:22][C:23]([OH:25])=[O:24])=[CH:19][CH:20]=1)=[C:3]([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:2]([CH3:1])=[CH:11]2

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 68534816[(4-{[3-Methyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}phenyl)oxy]acetic acid

Product 1

HCID 59014504({4-[(6-Hydroxy-3-methyl-2-phenyl-1-naphthalenyl)oxy]phenyl}oxy)acetic acidYield 19.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold (5° C.) solution of ([(4-{[3-methyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}phenyl)oxy]acetic acid (235) (0.150 g, 0.36 mmol) in CH2Cl2 (5 mL) was added BBr3 (0.1 mL, 1.1 mmol) slowly. The reaction mixture was stirred between 5° C. and 20° C. for 2 h and poured into 10% aqueous NaHCO3 (60 mL) slowly. The reaction mixture was extracted with EtOAc (3×75 mL). The combined organic layer was washed with brine (1×50 mL), dried (Na2SO4), and concentrated to afford the crude product. Purification by flash column chromatography using CHCl3 and MeOH as an eluent gave 0.028 g (19%) of the title compound (236) as an off-white solid. A 0.058 g of 5-[(4-hydroxyphenyl)oxy]-7-methyl-6-phenyl-2-naphthalenol was also isolated. 1H NMR (400 MHz, CDCl3): δ 7.62 (d, J=8.8 Hz, 1H), 7.46 (s, 1H), 7.26-7.18 (m, 3H), 7.12-7.09 (m, 2H), 6.92 and 6.90 (dd, J1=8.8 Hz, J2=2.4 Hz, 1H), 6.65 (d, J=9.2 Hz, 2H), 6.50 (d, J=8.8 Hz, 2H), 4.29 (s, 2H), 2.17 (s, 3H). LCMS (ESI) m/z 401.35 (M+H)+.

Workup

  1. extractionThe reaction mixture was extracted with EtOAc (3×75 mL)
  2. washThe combined organic layer was washed with brine (1×50 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customto afford the crude product
  6. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-96f5835ef4624cb68c503a6695ea153f
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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