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

HRID 1798211Notes

Reaction equation

HRID 1798211 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].C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:26]1[CH:31]=[N:30][CH:29]=[CH:28][N:27]=1.Cl>CN(C=O)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:26]3[CH:31]=[N:30][CH:29]=[CH:28][N:27]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 73277ChloropyrazineHCID 58292549Ethyl 2-(1,6-dihydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate

Product 1

HCID 58292868[1-Hydroxy-4-methyl-6-(pyrazin-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl esterYield 38.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °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 (0.5 g, 2.0 mmol) in anhydrous DMF (5 mL) were added Cs2CO3 (1.629 g, 5.0 mmol) and 2-chloro-pyrazine (0.275 g, 2.4 mmol) at room temperature. The reaction mixture was heated to 90° C. for 3 hours then poured into ice-water (10 mL). The mixture was acidified to pH 2 using dilute hydrochloric acid and extracted with ethyl acetate. The organic extracts were dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (EtOAc/hexane/AcOH=3:2:trace) to give the product as an oil (0.250 g, 38.1%). 1HNMR (400 MHz, DMSO-d6) δ9.22 (s, 1H), 8.53 (d, J=1.17 Hz, 1H), 8.35 (d, J=2.64 Hz, 1H), 8.18 (dd, J=2.78, 1.32 Hz, 1H), 7.25 (d, J=2.05 Hz, 1H), 7.10 (d, J=1.46 Hz, 1H), 5.53 (dd, J=9.08, 2.34 Hz, 1H), 3.94-4.11 (m, 2H), 3.13 (dd, J=15.52, 2.63 Hz, 1H), 2.20-2.40 (m, 4H), 1.06-1.26 (m, 3H). MS (ESI) m/z=329 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic extracts were dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel flash column chromatography (EtOAc/hexane/AcOH=3:2:trace)

Sources & evidence

ORD record
ord-12cf61dac2cb4f2594dd4fdf9f26262d
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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