Trimethyl borate → [4-(Morpholine-4-carbonyl)phenyl]boronic acid

HRID 2410746Notes

Reaction equation

HRID 2410746 reaction equation
C([Mg]Cl)(C)C.CN(C)CCOCCN(C)C.I[C:18]1[CH:23]=[CH:22][C:21]([C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[O:25])=[CH:20][CH:19]=1.[B:32](OC)([O:35]C)[O:33]C>C1COCC1>[N:26]1([C:24]([C:21]2[CH:22]=[CH:23][C:18]([B:32]([OH:35])[OH:33])=[CH:19][CH:20]=2)=[O:25])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 8470Trimethyl borateHCID 18204Bis(dimethylaminoethyl) etherHCID 7726344-[(4-Iodophenyl)carbonyl]morpholineHCID 178418918HCID 178418918, compound2×

Product 1

HCID 2773546[4-(Morpholine-4-carbonyl)phenyl]boronic acidYield 79.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Isopropylmagnesium chloride (27.8 mL, 2 M in THF, 55.6 mmol) was added to a solution of bis(2-dimethylaminoethyl)ether (10.5 mL, 55.6 mmol) in THF (230 mL) 15° C. After 20 minutes, (4-iodophenyl)-(morpholino)methanone (14.7 g, 46.4 mmol) was added and the reaction was removed from the cooling bath. After 1 hr, another 0.8 eq of isopropylmagnesium chloride was added. Trimethyl borate (10.6, 93 mmol) was added after 15 minutes, and after stirring 40 min, the reaction was quenched with 150 ml 1 N aqueous HCl. After stirring at room temperature for 2 hr, THF was removed on the rotary evaporator and the residue was extracted three times with EtOAc. The organic extracts were dried with Na2SO4. The solvent was removed and the residue was twice suspended in toluene and the solvent removed on the rotary evaporator. The resulting white solid was suspended in hexane and this was heated at reflux for 5 minutes. After cooling to room temperature, the white solid was collected by filtration and air-dried to afford 4-(morpholine-4-carbonyl)phenylboronic acid (8.7 g). MS (ESI) m/z 236.1 (M+H). 1H NMR (MeOD) δ ppm 7.78 (2H, d, J=7.30 Hz), 7.36 (2H, d, J=8.06 Hz), 3.72-3.41 (8H, m).

Workup

  1. customthe reaction was removed from the cooling bath
  2. waitAfter 1 hr
  3. customthe reaction was quenched with 150 ml 1 N aqueous HCl
  4. stirringAfter stirring at room temperature for 2 hr
  5. customTHF was removed on the rotary evaporator
  6. extractionthe residue was extracted three times with EtOAc
  7. dry with materialThe organic extracts were dried with Na2SO4
  8. customThe solvent was removed
  9. customthe solvent removed on the rotary evaporator
  10. temperaturethis was heated
  11. temperatureat reflux for 5 minutes
  12. filtrationthe white solid was collected by filtration
  13. customair-dried

Sources & evidence

ORD record
ord-20adb95f15a94df393d9342b5ec12ad2
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

Loading…