Hydrochloric Acid → [1-Hydroxy-4-methyl-6-([1,3,4]thiadiazol-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid

HRID 1798291Notes

Reaction equation

HRID 1798291 reaction equation
C([O:3][C:4](=[O:23])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[S:19][CH:20]=[N:21][N:22]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)C.[Li+].[OH-].Cl>C1COCC1.O.O>[OH:11][B:9]1[C:8]2[CH:12]=[C:13]([O:17][C:18]3[S:19][CH:20]=[N:21][N:22]=3)[CH:14]=[C:15]([CH3:16])[C:7]=2[CH:6]([CH2:5][C:4]([OH:23])=[O:3])[O:10]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 58292715[1-Hydroxy-4-methyl-6-([1,3,4]thiadiazol-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester

Product 1

HCID 58292783[1-Hydroxy-4-methyl-6-([1,3,4]thiadiazol-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acidYield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of [1-hydroxy-4-methyl-6-([1,3,4]thiadiazol-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (0.17 g, 0.5 mmol) in THF:H2O (1:1, 10 mL) at 0° C. was added a solution of LiOH (0.024 g, 1.01 mmol) in water (1 mL). The solution was allowed to warm to room temperature over 3 hours then acidified to pH 2 with 1N HCl (1 mL) at 0° C. The mixture was extracted with EtOAc (2×10 mL) and the organic extracts washed with water (10 mL), dried and concentrated in vacuo. The residue was purified by preparative HPLC to give [1-hydroxy-4-methyl-6-([1,3,4]thiadiazol-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid (0.15 g, 96%). 1H NMR (400 MHz, DMSO): δ 9.24 (s, 1H), 9.15 (s, 1H), 7.43 (s, 1H), 7.30 (s, 1H), 5.51 (d, J=6.8 Hz, 1H), 3.06 (d, J=15.6 Hz, 1H), 2.30 (s, 3H), 2.18-2.12 (m, 1H). MS (ESI) m/z=305 [M−H]−.

Workup

  1. extractionThe mixture was extracted with EtOAc (2×10 mL)
  2. washthe organic extracts washed with water (10 mL)
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-de8e2250f02b4801bf01687bd242c4c0
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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