Sodium hydride → HCID 66617711, compound

HRID 2403372Notes

Reaction equation

HRID 2403372 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[F:8].[H-].[Na+].[CH3:12][O:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Br)=[CH:16][CH:15]=1>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:18][C:17]2[CH:20]=[CH:21][C:14]([O:13][CH3:12])=[CH:15][CH:16]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1650214-Methoxybenzyl bromideHCID 27833813-Bromo-4-Fluorophenol

Product 1

HCID 66617711HCID 66617711, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-bromo-4-fluorophenol (0.59 g) in tetrahydrofuran (7 ml) under nitrogen was added sodium hydride, 60% dispersion in mineral oil (0.13 g). The solution was stirred at room temperature. After 30 minutes a solution of 4-methoxybenzylbromide (0.62 g) was added in tetrahydrofuran (5 ml). The reaction mixture was stirred at 50° C. overnight. The reaction mixture was partitioned between dichloromethane and brine, then dried (MgSO4), the solvents were removed in vacuo to give a crude residue. This crude residue was purified using flash chromatography to give 2-bromo-1fluoro-4-(4-methoxy-benzyloxy)-benzene (0.71 g). To a solution of 2-bromo-1fluoro-4-(4-methoxy-benzyloxy)-benzene (0.33 g) in tetrahydrofuran (10 ml) under nitrogen was added triisopropylborate (0.29 ml). The mixture was cooled to −78° C. and 2.5M n-butyllithium solution in hexanes was added. The reaction mixture was stirred at −40° C. for 1 hour, then warmed to 20° C. and quenched with 2M hydrochloric acid (aq) (2 ml). The reaction mixture was warmed to room temperature and stirred for 1 hour. The reaction mixture was adjusted to pH 7 using saturated sodium bicarbonate solution, then partitioned between ethyl acetate and water, dried (MgSO4) and the solvents removed in vacuo to yield a crude residue (0.31 g). A mixture of this crude residue and pinacol (0.25 g) in toluene (10 ml) were stirred under reflux overnight in a Dean-Stark apparatus. The solvents were removed in vacuo, the residue was then partitioned between ethyl acetate and water, the combined organics were washed with water then brine and dried (MgSO4), the solvents were removed in vacuo to yield 2-[2-fluoro-5-(4-methoxy-benzyloxy-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxyborolane (0.28 g)

Workup

  1. stirringThe reaction mixture was stirred at 50° C. overnight
  2. customThe reaction mixture was partitioned between dichloromethane and brine
  3. dry with materialdried (MgSO4)
  4. customthe solvents were removed in vacuo
  5. customto give a crude residue
  6. customThis crude residue was purified

Sources & evidence

ORD record
ord-de0fbd0453974683886614425ff0f948
Source dataset
uspto-grants-2014_08
Patent number
US08802670B2

Reaction notes

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