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

HRID 69821Notes

Reaction equation

HRID 69821 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.C(=O)(O)[O-].[Na+].CCCCCCC>ClCCl.O>[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

7

Reactant 4

HCID 8900HeptaneHCID 25134Boron tribromideHCID 516892Sodium Bicarbonate2×HCID 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 729.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(3-bromo-4-fluorophenyl)-3-(4-(2-methoxyethylamino)-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one (can be prepared according to Example 1, steps A-G; 1232 g, 3.08 mol) in dichloromethane (12 L) stirring in a 22 L flask at 0° C. was added boron tribromide (354 mL, 3.67 mL) dropwise at a rate so that the temperature did not exceed 10° C. After stirring on ice for 1 h, a solution of saturated aqueous sodium bicarbonate (2 L) was carefully added at a rate so that the temperature did not exceed 20° C. (addition time 10 min). The resulting mixture was transferred to a 50 L separatory funnel, diluted with water (10 L), and the pH of the aqueous layer adjusted from 1 to 8 using solid sodium bicarbonate. The layers were separated, and the organic layer was washed with water (10 L), and the solvents removed in vacuo to afford a tan solid (24 mol processed in multiple runs, 9.54 kg, quant. yield). The material was slurried in 4 volumes of 7:1 heptane:ethyl acetate (4×22 L flasks), filtered, and dried to furnish the title compound as a tan solid (8679 g, 94%). The product was a mixture of the hydroxy- and the corresponding bromo-species.

Workup

  1. customdid not exceed 10° C
  2. customdid not exceed 20° C.
  3. addition(addition time 10 min)
  4. customThe resulting mixture was transferred to a 50 L separatory funnel
  5. customThe layers were separated
  6. washthe organic layer was washed with water (10 L)
  7. customthe solvents removed in vacuo
  8. customto afford a tan solid (24 mol processed in multiple runs, 9.54 kg, quant. yield)
  9. filtrationethyl acetate (4×22 L flasks), filtered
  10. customdried

Sources & evidence

ORD record
ord-363cc73a6a1c4ba98896e19afc90cd31
Source dataset
uspto-grants-2014_09
Patent number
US08822511B2

Reaction notes

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