Trimethyl borate → (5-(Methoxymethyl)pyridin-3-yl)boronic acid

HRID 609632Notes

Reaction equation

HRID 609632 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[C:11]([CH2:13][O:14][CH3:15])[CH:12]=1.[B:16](OC)([O:19]C)[O:17]C.[OH-].[Na+]>CCCCCC.C(OCC)C.O>[CH3:15][O:14][CH2:13][C:11]1[CH:12]=[C:7]([B:16]([OH:19])[OH:17])[CH:8]=[N:9][CH:10]=1

Participants

8

Reactant 4

HCID 8470Trimethyl borateHCID 14798Sodium HydroxideHCID 186245693-Bromo-5-(methoxymethyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 19599757(5-(Methoxymethyl)pyridin-3-yl)boronic acidYield 10%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-100 °C

Procedure

To a solution of n-butyl lithium in hexane (6 ml of a 1.6M solution) in diethyl ether (40 ml) at -100° C. under nitrogen was added dropwise 3-bromo-5-methoxymethylpyridine (1.2 g, 6 mmol) (WO 95/28400) in diethyl ether (20 ml). After stirring for 45 minutes at -100° C., trimethyl borate (1.1 ml, 9.8 mmol) was added and the reaction mixture stirred at -100° C. for an extra 75 minutes. Water was added followed by 4N aqueous sodium hydroxide when the temperature reached 10° C. The aqueous layer was decanted, acidified to pH 5 with 2N aqueous hydrochloric acid and extracted 5 times with dichloromethane. The combined organics were dried (sodium sulphate) and evaporated to give the title compound as an oil (100 mg, 10%). MS, m/z 168 for (M+H)+. Rf 0.05 in ammonia/methanol/dichloromethane (1/10/90) on silica plate.

Workup

  1. stirringthe reaction mixture stirred at -100° C. for an extra 75 minutes
  2. customreached 10° C
  3. customThe aqueous layer was decanted
  4. extractionextracted 5 times with dichloromethane
  5. dry with materialThe combined organics were dried (sodium sulphate)
  6. customevaporated

Sources & evidence

ORD record
ord-7ad726563c2f48559b73c111e86145fa
Source dataset
uspto-grants-1999_12
Patent number
US05998416

Reaction notes

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