Triethylamine → 2-Chloro-4-fluoro-N-(1-hydroxy-3,3-dimethyl-1,3-dihydro-benzo[c][1,2]oxaborol-6-yl)-benzamide

HRID 60552Notes

Reaction equation

HRID 60552 reaction equation
[CH3:1][C:2]1([CH3:15])[O:6][B:5]([OH:7])[C:4]2[CH:8]=[C:9]([N+:12]([O-])=O)[CH:10]=[CH:11][C:3]1=2.CCN(CC)CC.[Cl:23][C:24]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:25]=1[C:26](Cl)=[O:27].CCOC(C)=O.Cl>C1COCC1.[Pd]>[Cl:23][C:24]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:25]=1[C:26]([NH:12][C:9]1[CH:10]=[CH:11][C:3]2[C:2]([CH3:15])([CH3:1])[O:6][B:5]([OH:7])[C:4]=2[CH:8]=1)=[O:27]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27365462-Chloro-4-fluorobenzoyl chlorideHCID 21866389Hydrogen chloride-ethyl acetateHCID 583730633,3-dimethyl-6-nitrobenzo[c][1,2]oxaborol-1(3H)-ol

Product 1

HCID 673597852-Chloro-4-fluoro-N-(1-hydroxy-3,3-dimethyl-1,3-dihydro-benzo[c][1,2]oxaborol-6-yl)-benzamideYield 91.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3,3-dimethyl-6-nitro-3H-benzo[c][1.2]oxaborol-1-ol (500 mg, 2.4 mmol) in THF (60 mL) was pass through H-Cube equipped with a 10% Pd/C Catcart (30×4 mm). The flow rate was set at 1.0 mL/min and TLC indicated complete consumption of starting material after one run. To the obtained light yellow solution was added Et3N (1.1 mL, 7.7 mmol, 3.2 equiv.), followed by drop wise addition of 2-cloro-4-fluoro-benzoyl chloride (0.51 mL, 3.8 mmol, 1.6 equiv.). The mixture was allowed to stir at room temperature over 18 h before poured into a 1:1 mixture of EtOAc/HCl (1 N). The layers were separated and the aqueous phase was extracted with EtOAc (3×). Combined organics was washed with H2O, brine and concentrated under reduced pressure to give a white solid. The solid was dissolved in minimal amount of THF and treated with heptanes. The precipitate was collected by filtration and washed with heptanes to give the title compound as a white solid. LCMS (M/Z): 334 (M+H); 1H NMR (DMSO-d6) δ: 10.49 (s, 1H), 9.06 (s, 1H), 8.01 (d, J=1.7 Hz, 1H), 7.60-7.65 (m, 2H), 7.55 (dd, J=9.0, 2.5 Hz, 1H), 7.28-7.37 (m, 2H), 1.40 (s, 6H). Amount obtained: 726 mg, (91.2% yield).

Workup

  1. customconsumption of starting material after one run
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc (3×)
  4. washCombined organics was washed with H2O, brine
  5. concentrationconcentrated under reduced pressure
  6. customto give a white solid
  7. filtrationThe precipitate was collected by filtration
  8. washwashed with heptanes

Sources & evidence

ORD record
ord-d58a00c62d08420ca2a712420e9fc3b4
Source dataset
uspto-grants-2016_09
Patent number
US09440994B2

Reaction notes

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