Ammonium Chloride → (2-(Benzyloxy)biphenyl-3-yl)(2'-methoxybiphenyl-3-yl)(phenyl)methanol

HRID 45461Notes

Reaction equation

HRID 45461 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH3:15])[CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[CH2:21]([O:28][C:29]1[C:34]([C:35]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:36])=[CH:33][CH:32]=[CH:31][C:30]=1[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:21]([O:28][C:29]1[C:34]([C:35]([C:2]2[CH:3]=[C:4]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[O:14][CH3:15])[CH:5]=[CH:6][CH:7]=2)([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[OH:36])=[CH:33][CH:32]=[CH:31][C:30]=1[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 186686213'-Bromo-2-methoxybiphenylHCID 58238523(2-(Benzyloxy)biphenyl-3-yl)(phenyl)methanoneHCID 178418339Butyllithium

Product 1

HCID 58238602(2-(Benzyloxy)biphenyl-3-yl)(2'-methoxybiphenyl-3-yl)(phenyl)methanolYield 16.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3′-bromo-2-methoxybiphenyl (1.08 g, 4.1 mmol) in anhydrous tetrahydrofuran (10 mL) was stirred at −78° C. and 2.5M n-butyllithium in hexanes (1.64 mL, 4.1 mmol) was added at such a rate that the temperature did nor exceed −70° C. Stirring was continued at −78° C. for 1 hr. A solution of 25 (1.5 g, 4.1 mmol) in tetrahydrofuran (6 mL) was added at such a rate that the temperature did not exceed −65° C. Stirring was continued at −78° C. for 20 min and at room temperature for 2 hr. The reaction mixture was poured onto saturated ammonium chloride (150 mL) and extracted with ethyl acetate (150 mL). The organic extract was washed with water (2×80 mL). The organic layer was dried over sodium sulfate, filtered and the solvent was removed on a rotary evaporator. The crude product was purified by chromatography on silica (80 g) with 2% ethyl acetate in heptane (4 L). Pure 26 (0.87 g) and slightly impure 26 (0.38 g) were isolated (total yield 55%).

Workup

  1. customexceed −70° C
  2. customdid not exceed −65° C
  3. stirringStirring
  4. waitwas continued at −78° C. for 20 min and at room temperature for 2 hr
  5. extractionextracted with ethyl acetate (150 mL)
  6. extractionThe organic extract
  7. washwas washed with water (2×80 mL)
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. customthe solvent was removed on a rotary evaporator
  11. customThe crude product was purified by chromatography on silica (80 g) with 2% ethyl acetate in heptane (4 L)

Sources & evidence

ORD record
ord-a152dac435c44e6a8b983db5d87ef6bf
Source dataset
uspto-grants-2013_09
Patent number
US08541522B2

Reaction notes

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