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Trimethyl borate → 5-Fluoro-2-(tetrahydropyran-2-yloxy)benzeneboronic acid

HRID 13639
Notes
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Reaction equation

HRID 13639 reaction equation
[Mg].Br[C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[O:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1.[B:17](OC)([O:20]C)[O:18]C.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.O>[F:9][C:7]1[CH:6]=[CH:5][C:4]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:3]([B:17]([OH:20])[OH:18])[CH:8]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 8470Trimethyl borateHCID 11430Potassium CarbonateHCID 5462224MagnesiumHCID 593402472-(2'-Bromo-4-fluorophenoxy)tetrahydro-2H-pyran

Product 1

HCID 593402105-Fluoro-2-(tetrahydropyran-2-yloxy)benzeneboronic acid

Reagents, catalysts & solvents 2

HCID 962
Water
Solvent
HCID 8028TetrahydrofuranSolvent2×

Procedure

48.6 g (2.00 mol) of magnesium and 510 g (1.85 mol) of 2-bromo-4-fluoro-1-(tetrahydropyran-2-yloxy)benzene in 1250 ml of THF were used to prepare a Grignard reagent. This Grignard reagent was slowly added dropwise at −78° C. to a mixture of 241.6 ml (2.00 mol) of trimethyl borate in 500 ml of THF. On completion of addition, the reaction mixture was allowed to warm to room temperature and was hydrolyzed by addition of 100 ml of saturated potassium carbonate solution and 1000 ml of water. The organic phase was washed with saturated sodium chloride, solution. (1×500 ml) and subsequently concentrated to dryness. The yield was 428.2 g (1.78 mol), and the product was obtained as a waxy solid which contained varying proportions of boronic anhydride and borinic acids and was used in the following stage without further purification.

Workup

  1. additionOn completion of addition
  2. washThe organic phase was washed with saturated sodium chloride, solution
  3. concentration(1×500 ml) and subsequently concentrated to dryness
  4. customThe yield was 428.2 g (1.78 mol), and the product was obtained as a waxy solid which
  5. customwas used in the following stage without further purification

Sources & evidence

ORD record
ord-e6a0ec2d83bb48dc9cb8301c94645b0c
Source dataset
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07728137B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes