Hydrochloric Acid → 3-Fluoro-2-(1-hydroxypropyl)phenylboronic acid

HRID 251651Notes

Reaction equation

HRID 251651 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:8]=1[CH:14]([OH:17])[CH2:15][CH3:16].[B:18](OC(C)C)([O:23]C(C)C)[O:19]C(C)C.Cl>CCCCC.C1COCC1>[F:13][C:9]1[C:8]([CH:14]([OH:17])[CH2:15][CH3:16])=[C:7]([B:18]([OH:23])[OH:19])[CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 21531Triisopropyl borateHCID 580898611-(2-Bromo-6-fluoro-phenyl)-propan-1-olHCID 178418339Butyllithium

Product 1

HCID 580898533-Fluoro-2-(1-hydroxypropyl)phenylboronic acid

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of n-BuLi (2.15 mL, 4.3 mmol) in pentane (2 M) is added dropwise to a solution of 1-(2-bromo-6-fluoro-phenyl)-propan-1-ol (500 mg, 2.15 mmol) in THF at −78° C. The mixture is stirred for 2 hours at −78° C. (i-PrO)3B (41 mL, 4.3 mmol) is added in one portion and the mixture is warmed slowly to room temperature and stirred for 12 hours. 1N HCl (10 mL) is added and the mixture is stirred for 2 hours at room temperature. The organic layer is separated and the aqueous layer is extracted with DCM (3×30 mL). The combined organic layers are dried and solvents are removed in vacuo. The crude product is purified by PTLC eluting with 5% MeOH in DCM to give 3-fluoro-2-(1-hydroxypropyl)phenylboronic acid.

Workup

  1. additionis added in one portion
  2. stirringthe mixture is stirred for 2 hours at room temperature
  3. customThe organic layer is separated
  4. extractionthe aqueous layer is extracted with DCM (3×30 mL)
  5. customThe combined organic layers are dried
  6. customsolvents are removed in vacuo
  7. customThe crude product is purified by PTLC
  8. washeluting with 5% MeOH in DCM

Sources & evidence

ORD record
ord-59768b12abf5442abcfd9f3a0d10beeb
Source dataset
uspto-grants-2011_01
Patent number
US07863454B2

Reaction notes

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