Morpholine → 3-Fluoro-4-(morpholine-4-carbonyl)phenylboronic acid

HRID 1874003Notes

Reaction equation

HRID 1874003 reaction equation
[B:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[C:6]([F:13])[CH:5]=1)([OH:3])[OH:2].[NH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C>[F:13][C:6]1[CH:5]=[C:4]([B:1]([OH:2])[OH:3])[CH:12]=[CH:11][C:7]=1[C:8]([N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)=[O:10]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 27632014-Carboxy-3-fluorophenylboronic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 576184153-Fluoro-4-(morpholine-4-carbonyl)phenylboronic acidYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-borono-2-fluorobenzoic acid (1.000 g, 5.44 mmol), morpholine (0.951 mL, 10.87 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.103 g, 5.53 mmol) in DMF (10 mL) was stirred at room temperature for 16 h and quenched with 1 N HCl (20 mL). Attempted extraction with EtOAc did not remove all of the product from aqueous phase. The two phases were combined, concentrated and purified by reverse phase HPLC (Sunfire S10 30×250 mm column, 30-45% solvent B gradient) to give the expected product as white solid (1.2385 g, 90% yield). MS (ES+) m/z: 254 (M+H); LC retention time: 2.06 min (analytical HPLC Method A).

Workup

  1. customquenched with 1 N HCl (20 mL)
  2. extractionextraction with EtOAc
  3. customdid not remove all of the product from aqueous phase
  4. concentrationconcentrated
  5. custompurified by reverse phase HPLC (Sunfire S10 30×250 mm column, 30-45% solvent B gradient)

Sources & evidence

ORD record
ord-494752a6a5fe4662afb92f94c6b449f5
Source dataset
uspto-grants-2012_11
Patent number
US08304539B2

Reaction notes

Loading…