Hydrochloric Acid → 2-(6-(Ethoxycarbonyloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl) acetic acid

HRID 1798132Notes

Reaction equation

HRID 1798132 reaction equation
[OH:1][B:2]1[C:6]2[CH:7]=[C:8]([OH:12])[CH:9]=[C:10]([CH3:11])[C:5]=2[CH:4]([CH2:13][C:14]([OH:16])=[O:15])[O:3]1.[OH-].[Na+].Cl[C:20]([O:22][CH2:23][CH3:24])=[O:21].Cl>O>[CH2:23]([O:22][C:20]([O:12][C:8]1[CH:9]=[C:10]([CH3:11])[C:5]2[CH:4]([CH2:13][C:14]([OH:16])=[O:15])[O:3][B:2]([OH:1])[C:6]=2[CH:7]=1)=[O:21])[CH3:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 582927912-(1,6-Dihydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetic acid

Product 1

HCID 582928622-(6-(Ethoxycarbonyloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl) acetic acidYield 36.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To the suspension of crude 2-(1,6-dihydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetic acid (250 mg, 1.126 mmol) in 2 ml H2O was added NaOH (90 mg, 2.25 mmol) in 6 ml H2O, followed by ethyl chloroformate (134.4 mg, 1.24 mmol) dropwise. The reaction mixture was stirred at room temperature for 20 min and acidified by 1N HCl to pH=5.0. The mixture was extracted with EtOAc (3×20 mL) and the combined organic layers were dried over anhydrous Na2SO4 and concentrated to dryness. The residue was purified by prep HPLC to give the title compound as an off-white powder (120.5 mg, yield: 34%, two steps). 1H NMR (400 MHz, DMSO) δ 12.37-12.36 (t, J=3.6 Hz, 1H), 9.29 (s, 1H), 7.30 (d, J=2.0 Hz, 1H), 7.14 (d, J=2.0 Hz, 1H), 5.53-5.50 (m, 1H), 4.28-4.22 (m, 2H), 3.10-3.05 (m, 1H), 2.31 (s, 3H), 2.11-2.17 (m, 1H), 1.32-1.27 (m, 3H); MS (ESI) m/z=285 [M+H]+.

Workup

  1. extractionThe mixture was extracted with EtOAc (3×20 mL)
  2. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  3. concentrationconcentrated to dryness
  4. customThe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-7f5c362bf6804112b687daf84a82635a
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

Loading…