Ammonium Chloride → (2-(Benzyloxy)-3-tert-butylphenyl)(2-methoxybiphenyl-3-yl)(phenyl)methanol

HRID 1042519Notes

Reaction equation

HRID 1042519 reaction equation
Br[C:2]1[C:3]([O:14][CH3:15])=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[CH2:21]([O:28][C:29]1[C:34]([C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:33][CH:32]=[CH:31][C:30]=1[C:39]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:40])[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]([CH3:38])([CH3:37])[CH3:36])=[CH:33][CH:32]=[CH:31][C:30]=1[C:39]([C:2]1[C:3]([O:14][CH3:15])=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1)([C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[OH:40])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 183474973-Bromo-2-methoxy-1,1'-biphenylHCID 58238504(2-(Benzyloxy)-3-tert-butylphenyl)(phenyl)methanoneHCID 178418339Butyllithium

Product 1

HCID 58238509(2-(Benzyloxy)-3-tert-butylphenyl)(2-methoxybiphenyl-3-yl)(phenyl)methanolYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-bromo-2-methoxybiphenyl (1.18 g, 4.5 mmol) in anhydrous tetrahydrofuran (20 mL) was stirred under nitrogen at −78° C. and 2.5 M n-butyllithium in hexanes (1.8 mL, 4.5 mmol) was added at such a rate that the temperature did not exceed −70° C. Stirring was continued on the cold bath for 20 min and a solution of 14 (1.55 g, 4.5 mmol) in dry tetrahydrofuran (8 mL) was added at such a rate that the temperature did not exceed −65° C. Stirring was continued on the cold bath for 30 min then the reaction mixture was allowed to reach room temperature and stirred for 2 hr. The reaction mixture was poured on saturated ammonium chloride (150 mL) and extracted with ethyl acetate (180 mL). The organic extract was washed with water (2×80 mL), dried over sodium sulfate and stripped. The crude product was purified by chromatography on silica (85 g) with 0.2% ethyl acetate in heptane (6 L). Pure 15 (1.02 g, 43%) was isolated.

Workup

  1. customdid not exceed −70° C
  2. customdid not exceed −65° C
  3. stirringStirring
  4. waitwas continued on the cold bath for 30 min
  5. customto reach room temperature
  6. stirringstirred for 2 hr
  7. extractionextracted with ethyl acetate (180 mL)
  8. extractionThe organic extract
  9. washwas washed with water (2×80 mL)
  10. dry with materialdried over sodium sulfate
  11. customThe crude product was purified by chromatography on silica (85 g) with 0.2% ethyl acetate in heptane (6 L)

Sources & evidence

ORD record
ord-255d837fd15f4936bb2c793146a0d6ad
Source dataset
uspto-grants-2013_10
Patent number
US08557936B2

Reaction notes

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