Boron tribromide → 4-[(4-Bromo-2-furyl)methyl]-3-{4-[(2-hydroxyethyl)amino]-1,2,5-oxadiazol-3-yl}-1,2,4-oxadiazol-5(4H)-one

HRID 2402246Notes

Reaction equation

HRID 2402246 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:7][N:8]2[C:12](=[O:13])[O:11][N:10]=[C:9]2[C:14]2[C:18]([NH:19][CH2:20][CH2:21][O:22]C)=[N:17][O:16][N:15]=2)[O:5][CH:6]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl.O>[Br:1][C:2]1[CH:3]=[C:4]([CH2:7][N:8]2[C:12](=[O:13])[O:11][N:10]=[C:9]2[C:14]2[C:18]([NH:19][CH2:20][CH2:21][OH:22])=[N:17][O:16][N:15]=2)[O:5][CH:6]=1

Participants

6

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 666051744-[(4-Bromo-2-furyl)methyl]-3-{4-[(2-methoxyethyl)amino]-1,2,5-oxadiazol-3-yl}-1,2,4-oxadiazol-5(4H)-one

Product 1

HCID 666059514-[(4-Bromo-2-furyl)methyl]-3-{4-[(2-hydroxyethyl)amino]-1,2,5-oxadiazol-3-yl}-1,2,4-oxadiazol-5(4H)-oneYield 98.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

In a round bottom flask under nitrogen atmosphere, 4-[(4-bromo-2-furyl)methyl]-3-{4-[(2-methoxyethyl)amino]-1,2,5-oxadiazol-3-yl}-1,2,4-oxadiazol-5(4H)-one (8.2 g, 21 mmol) was stirred in dichloromethane (68 mL). The temperature was brought to −78° C. and a solution of 1.0 M boron tribromide in dichloromethane (43 mL, 43 mmol) was added dropwise over 45 minutes. The reaction stirred at −78° C. for 45 minutes and continued to stir at 0° C. for an additional 30 minutes. While remaining at 0° C., a saturated solution of sodium bicarbonate in water (120 mL) was added dropwise over 25 minutes. After warming to room temperature, the organic layer was collected and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate and concentrated in vacuo to give the desired product (7.7 g, 97%) along with a small amount of 3-{4-[(2-bromoethyl)amino]-1,2,5-oxadiazol-3-yl}-4-[(4-bromo-2-furyl)methyl]-1,2,4-oxadiazol-5(4H)-one. LCMS calculated for C11H11BrN5O5 (M+H)+: m/z=371.7, 374.0. 1H NMR (400 MHz, DMSO-d6): δ 7.89 (s, 1H), 6.68 (s, 1H), 6.31 (t, J=5.8 Hz, 1H), 5.08 (s, 2H), 4.85 (br s, 1H), 3.56 (m, 2H), 3.30 (q, J=5.6 Hz, 2H).

Workup

  1. customwas brought to −78° C.
  2. stirringto stir at 0° C. for an additional 30 minutes
  3. customWhile remaining at 0° C.
  4. temperatureAfter warming to room temperature
  5. customthe organic layer was collected
  6. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
  7. washThe combined organic layers were washed with brine (100 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f542aca9e0d247bf8da981723caba6ca
Source dataset
uspto-grants-2014_08
Patent number
US08796319B2

Reaction notes

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