Azetidine → [4-(Azetidine-1-carbonyl)phenyl]boronic acid

HRID 1873999Notes

Reaction equation

HRID 1873999 reaction equation
[B:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1)([OH:3])[OH:2].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2[N:25]=[CH:26][CH:27]=[CH:28]C=2N=N1.C(N(CC)C(C)C)(C)C.N1CCC1>CC#N>[N:25]1([C:8]([C:7]2[CH:6]=[CH:5][C:4]([B:1]([OH:2])[OH:3])=[CH:12][CH:11]=2)=[O:10])[CH2:26][CH2:27][CH2:28]1

Participants

6

Reactant 4

HCID 10422AzetidineHCID 81531DiisopropylethylamineHCID 3121834-Carboxyphenylboronic 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 57747385[4-(Azetidine-1-carbonyl)phenyl]boronic acidYield 55.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 4-boronobenzoic acid (527.4 mg, 3.18 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.61 g, 4.23 mmol) and N,N-diisopropylethylamine (1.665 mL, 9.53 mmol) in CH3CN (40 mL) was stirred at room temperature for 30 min. Azetidine (0.321 mL, 4.76 mmol) was added. After stirring for 3 days, the mixture was concentrated and purified by reverse phase HPLC (Sunfire S10 30×250 mm column, 10-40% solvent B gradient) to give the expected product as white solid (361 mg, 55% yield). 1H NMR (500 MHz, methanol-d4) δ ppm 7.68 (2H, d, J=7.70 Hz), 7.60 (2H, d, J=7.97 Hz), 4.37 (2H, t, J=7.56 Hz), 4.19 (2H, t, J=7.84 Hz), 2.36 (2H, quin); MS (ES+) m/z: 206 (M+H); LC retention time: 2.01 min (analytical HPLC Method A).

Workup

  1. concentrationthe mixture was concentrated
  2. custompurified by reverse phase HPLC (Sunfire S10 30×250 mm column, 10-40% solvent B gradient)

Sources & evidence

ORD record
ord-20086c809e144889b8a1b22dc3c4c148
Source dataset
uspto-grants-2012_11
Patent number
US08304539B2

Reaction notes

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