Hydrochloric Acid → Ethyl 2-(1-hydroxy-4-methyl-6-(5-nitro-1,3,4-thiadiazol-2-yloxy)-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate

HRID 1798292Notes

Reaction equation

HRID 1798292 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([OH:17])[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2].Br[C:20]1[S:21][C:22]([N+:25]([O-:27])=[O:26])=[N:23][N:24]=1.C([O-])([O-])=O.[K+].[K+].Cl>C(#N)C>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:20]3[S:21][C:22]([N+:25]([O-:27])=[O:26])=[N:23][N:24]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 122078702-Bromo-5-nitro-1,3,4-thiadiazoleHCID 58292549Ethyl 2-(1,6-dihydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate

Product 1

HCID 58292621Ethyl 2-(1-hydroxy-4-methyl-6-(5-nitro-1,3,4-thiadiazol-2-yloxy)-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of (1,6-dihydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester (2.55 g, 10.2 mmol) in anhydrous acetonitrile (150 mL) was added 2-bromo-5-nitro-[1,3,4]thiadiazole (3.0 g, 14.3 mmol) at 0° C. The reaction mixture was cooled to −20° C. and K2CO3 (9.87 g, 71.4 mmol) was added. After stirring at −20 to −25° C. for 3.5 days, the reaction mixture was acidified to pH 2 with dilute hydrochloric acid at 0° C. and extracted with EtOAc. The organic extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (EtOAc/hexanes/AcOH=2:1:trace) followed by recrystallization from methanol to give pure product as a white powder after lyophilization (1.35 g, 34.9%). 1HNMR (400 MHz, DMSO-d6) δ9.41 (s, 1H), 7.54 (d, J=2.34 Hz, 1H), 7.41 (d, J=1.76 Hz, 1H), 5.58 (dd, J=8.64, 2.78 Hz, 1H), 4.02 (q, J=7.22 Hz, 2H), 3.14 (dd, J=15.52, 2.63 Hz, 1H), 2.23-2.43 (m, 4H), 1.12 (t, 3H). MS (ESI) m/z=378 [M−H]−.

Workup

  1. extractionextracted with EtOAc
  2. washThe organic extracts were washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel flash column chromatography (EtOAc/hexanes/AcOH=2:1:trace)
  6. customfollowed by recrystallization from methanol
  7. customto give pure product as a white powder after lyophilization (1.35 g, 34.9%)

Sources & evidence

ORD record
ord-58822b0d6bb344659e48bd05fc86ac3b
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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