Hydrochloric Acid → HCID 58292708, compound

HRID 1798325Notes

Reaction equation

HRID 1798325 reaction equation
Cl[C:2]1[N:6]=[C:5]([O:7][C:8]2[CH:9]=[C:10]([CH3:22])[C:11]3[CH:15]([CH2:16][C:17]([OH:19])=[O:18])[O:14][B:13]([OH:20])[C:12]=3[CH:21]=2)[S:4][N:3]=1.[Li+].C[Si]([N-:28][Si](C)(C)C)(C)C.Cl>C1COCC1.O>[NH2:28][C:2]1[N:6]=[C:5]([O:7][C:8]2[CH:9]=[C:10]([CH3:22])[C:11]3[CH:15]([CH2:16][C:17]([OH:19])=[O:18])[O:14][B:13]([OH:20])[C:12]=3[CH:21]=2)[S:4][N:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 2733832Lithium Hexamethyldisilazide2×HCID 58292603HCID 58292603, compound

Product 1

HCID 58292708HCID 58292708, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [6-(3-chloro-[1,2,4]thiadiazol-5-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid (100 mg, 0.27 mmol) in THF (1.5 mL) was added LHMDS (1M in Hexanes, 0.54 mL, 0.54 mmol). The resulting solution was stirred at room temperature for overnight. LC-MS showed still half starting material left. The mixture was added LHMDS (1M in Hexanes, 0.54 mL, 0.54 mmol) again. After 3 hours, the mixture was diluted with H2O and acidified to pH 3 with 1N HCl at 0° C. The resulting mixture was extracted with ethyl acetate. The organic phase was separated, dried (Na2SO4), and concentrated. The crude mixture was purified by prep HPLC to give title compound (30 mg, 40%) as a white solid. 1H NMR (CD3OD) δ7.38 (d, 1H), 7.26 (d, 1H), 5.66 (dd, 1H), 3.16 (dd, 1H), 2.39 (s, 3H), 2.34 (dd, 1H). MS found: (M+H)+: 322.

Workup

  1. waitleft
  2. waitAfter 3 hours
  3. extractionThe resulting mixture was extracted with ethyl acetate
  4. customThe organic phase was separated
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude mixture was purified by prep HPLC

Sources & evidence

ORD record
ord-a605ffc2f35547d48e5340a1f32c0863
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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