Lithium hydroxide, monohydrate → 2-(6-(5-Amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)propanoic acid

HRID 1798312Notes

Reaction equation

HRID 1798312 reaction equation
[NH2:1][C:2]1[S:6][C:5]([O:7][C:8]2[CH:9]=[C:10]([CH3:25])[C:11]3[CH:15]([CH:16]([CH3:22])[C:17]([O:19]CC)=[O:18])[O:14][B:13]([OH:23])[C:12]=3[CH:24]=2)=[N:4][N:3]=1.O.[OH-].[Li+]>O.C1COCC1>[NH2:1][C:2]1[S:6][C:5]([O:7][C:8]2[CH:9]=[C:10]([CH3:25])[C:11]3[CH:15]([CH:16]([CH3:22])[C:17]([OH:19])=[O:18])[O:14][B:13]([OH:23])[C:12]=3[CH:24]=2)=[N:4][N:3]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 58292692Ethyl 2-(6-(5-amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)propanoate

Product 1

HCID 582927322-(6-(5-Amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)propanoic acid

Reagents, catalysts & solvents 1

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

Procedure

Into a 50-mL round-bottom flask was placed a solution of ethyl 2-(6-(5-amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)propanoate (500 mg, 1.32 mmol, 1.00 equiv, 96%) in H2O/THF (10/10 mL), then added lithium hydroxide hydrate (230 mg, 5.48 mmol, 4.00 equiv). The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The residual solution was adjusted to pH 3 with HCl (1 mol/L) and stirred for 30 min at room temperature. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by Prep-HPLC with the following conditions: Column, Xbridge Prep Phenyl, 5 μm, 19×150 mm; Mobile phase, water (with 0.05% TFA) and CH3CN; Gradient, 17% CH3CN up to 30% in 8 min, up to 100% in 1.5 min; Detector, UV 220 & 254 nm. This resulted in 30.2 mg (6%) of 2-(6-(5-amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)propanoic acid as a white solid. H-NMR (300 MHz, DMSO-d6, ppm): δ1.284 (3H, d, J=7.2 Hz), 2.332 (3H, s), 3.120 (2H, m), 5.301 (1H, d, J=2.7 Hz), 7.082-7.141 (3H, m), 7.295 (1H, d, J=2.1 Hz), 9.180 (1H, s). MS (ESI) m/z: 336 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. stirringstirred for 30 min at room temperature
  4. concentrationThe resulting mixture was concentrated under vacuum
  5. customThe crude product (200 mg) was purified by Prep-HPLC with the following conditions
  6. waitGradient, 17% CH3CN up to 30% in 8 min
  7. waitup to 100% in 1.5 min
  8. customThis resulted in 30.2 mg (6%) of 2-(6-(5-amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)propanoic acid as a white solid

Sources & evidence

ORD record
ord-50bbb5d391cb4456b14c2e50eae7c775
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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