Tetrahydrofuran → HCID 136377301, compound

HRID 2407501Notes

Reaction equation

HRID 2407501 reaction equation
C(N(CC)CC)C.[F:8][C:9]1[CH:14]=[C:13]([C:15]([OH:17])=O)[CH:12]=[CH:11][C:10]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.ClC(O[CH2:28][CH:29]([CH3:31])[CH3:30])=O.[OH:32][NH:33][C:34](=[NH:43])C1C=CC(CO)=CC=1.[O:44]1C[CH2:47][CH2:46][CH2:45]1>>[OH:32][N:33]=[C:34]([NH:43][C:15]([C:13]1[CH:12]=[CH:11][C:10]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:9]([F:8])[CH:14]=1)=[O:17])[C:31]1[CH:47]=[CH:46][C:45]([OH:44])=[CH:28][C:29]=1[CH3:30]

Participants

6

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 162174932-Fluorobiphenyl-4-carboxylic AcidHCID 178513316HCID 178513316, compound

Product 1

HCID 136377301HCID 136377301, compound

Conditions

Temperature
10 °C

Procedure

Triethylamine (52 mL, 0.373 mol) is added to a stirred solution of 2-fluorobiphenyl-4-carboxylic acid (40 g, 0.185 mol) in tetrahydrofuran (800 mL). The reaction mixture is cooled to 5-15° C., iso-butyl chloroformate (36.5 mL, 0.28 mol) is added over a period of 20 minutes and stirred for 2 hrs at 15-20° C. A solution of N-hydroxy-4-hydroxymethylbenzamidine (36.9 g, 0.22 mol) in tetrahydrofuran (400 mL) is added to the reaction mixture and stirred for 2 hrs at 20-25° C. The reaction mixture is concentrated under reduced pressure, demineralized water (400 mL) is added to the residue and stirred for one hour at 5-10° C. The slurry is filtered, washed with demineralized water (400 mL) and dried under reduced pressure. The solid is stirred in 5% aqueous sodium bicarbonate solution (600 mL), filtered, washed with demineralized water and dried under reduced pressure. Finally the solid is washed with cyclohexane (600 mL) and dried under reduced pressure at 40-50° C. to give 2-fluorobiphenyl-4-carboxylic acid [hydroxyimino(4-hydroxy-methylphenyl)methyl]amide.

Workup

  1. stirringstirred for 2 hrs at 20-25° C
  2. concentrationThe reaction mixture is concentrated under reduced pressure, demineralized water (400 mL)
  3. additionis added to the residue
  4. stirringstirred for one hour at 5-10° C
  5. filtrationThe slurry is filtered
  6. washwashed with demineralized water (400 mL)
  7. customdried under reduced pressure
  8. stirringThe solid is stirred in 5% aqueous sodium bicarbonate solution (600 mL)
  9. filtrationfiltered
  10. washwashed with demineralized water
  11. customdried under reduced pressure
  12. washFinally the solid is washed with cyclohexane (600 mL)
  13. customdried under reduced pressure at 40-50° C.

Sources & evidence

ORD record
ord-6b72166b58e64df2864e14ecabe6f4bd
Source dataset
uspto-grants-2014_08
Patent number
US08809539B2

Reaction notes

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