Bromide ion → 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 1798289Notes

Reaction equation

HRID 1798289 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:19][C:20]1[S:21][C:22]([N+:25]([O-:27])=[O:26])=[N:23][N:24]=1.C([O-])([O-])=O.[K+].[K+].[Br-]>>[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:22]3[S:21][C:20]([Br:19])=[N:24][N:23]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2].[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 259Bromide ionHCID 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 2

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)acetateYield 26%HCID 58292659[6-(5-Bromo-[1,3,4]thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl esterYield 14%

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 (1.5 g, 6.0 mmol) and 2-bromo-5-nitro-[1,3,4]thiadiazole (2.52 g, 12.0 mmol) at −20° C. was added K2CO3 (1.65 g, 12.0 mmol). The reaction mixture was stirred for 10 hours at −20° C. then concentrated in vacuo. The residue was dissolved in EtOAc (20 mL), washed with water (2×10 mL), dried and concentrated. The residue was purified by silica gel flash column chromatography to give a mixture of products (5:2 nitro:bromide, 1.6 g). This was further purified by preparative HPLC to give [6-(5-bromo-[1,3,4]thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (0.34 g, 14%) and [1-hydroxy-4-methyl-6-(5-nitro-[1,3,4]thiadiazol-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (0.6 g, 26%).

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc (20 mL)
  3. washwashed with water (2×10 mL)
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel flash column chromatography
  7. customto give
  8. customThis was further purified by preparative HPLC

Sources & evidence

ORD record
ord-45663afaa05a40189888827ffe8d40eb
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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