Boron tribromide → 4-(3-Bromo-4-fluorophenyl)-3-(4-((2-hydroxyethyl)amino)-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one

HRID 69817Notes

Reaction equation

HRID 69817 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[O:12][N:11]=[C:10]2[C:15]2[C:19]([NH:20][CH2:21][CH2:22][O:23]C)=[N:18][O:17][N:16]=2)[CH:5]=[CH:6][C:7]=1[F:8].B(Br)(Br)Br>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[O:12][N:11]=[C:10]2[C:15]2[C:19]([NH:20][CH2:21][CH2:22][OH:23])=[N:18][O:17][N:16]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 666056984-(3-bromo-4-fluorophenyl)-3-(4-(2-methoxyethylamino)-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one

Product 1

HCID 666056584-(3-Bromo-4-fluorophenyl)-3-(4-((2-hydroxyethyl)amino)-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-oneYield 99.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

4-(3-Bromo-4-fluorophenyl)-3-{4-[(2-methoxyethyl)amino]-1,2,5-oxadiazol-3-yl}-1,2,4-oxadiazol-5(4H)-one (78.4 g, 0.196 mol) was dissolved in dichloromethane (600 mL). At −67° C. boron tribromide (37 mL, 0.392 mol) was added over 15 min. The reaction was warmed up to −10° C. in 30 min. LCMS indicated reaction completed. The reaction was stirred at room temperature for 1 hour. At 0-5° C. the reaction was slowly quenched with saturated sodium bicarbonate solution (1.5 L) over 30 min. The reaction temperature rose to 25° C. The reaction was extracted with ethyl acetate (2×500 mL, first extraction organic layer is on the bottom and second extraction organic lager is on the top). The combined organic layers were dried over sodium sulfate and concentrated to give the desired product (75 g, 99%) as a crude brown solid. LCMS for C12H10BrFN5O4 (M+H)+: m/z=386.0, 388.0. 1H NMR (400 MHz, DMSO-d6): δ 8.08 (dd, J=6.2, 2.5 Hz, 1 H), 7.70 (m, 1 H), 7.68 (t, J=8.7 Hz, 1 H), 6.33 (t, J=5.6 Hz, 1 H), 4.85 (t, J=5.0 Hz, 1 H), 3.56 (dd, J=10.6, 5.6 Hz, 2 H), 3.29 (dd, J=11.5, 5.9 Hz, 2 H).

Workup

  1. customreaction
  2. customAt 0-5° C. the reaction was slowly quenched with saturated sodium bicarbonate solution (1.5 L) over 30 min
  3. customrose to 25° C
  4. extractionThe reaction was extracted with ethyl acetate (2×500 mL, first extraction organic layer
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f26205b3d8a3422eb7ce109e1f0e13b4
Source dataset
uspto-grants-2014_09
Patent number
US08822511B2

Reaction notes

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