3-Butyn-2-amine, 4-[3-(4-fluorophenoxy)phenyl]-N-hydroxy- → Fenleuton

HRID 861687Notes

Reaction equation

HRID 861687 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C:7]2[CH:8]=[C:9]([C:13]#[C:14][CH:15]([NH:17][OH:18])[CH3:16])[CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1.[N-:21]=[C:22]=[O:23].[K+]>C(OCC)(=O)C.O>[OH:18][N:17]([CH:15]([C:14]#[C:13][C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([O:6][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:20][CH:19]=2)[CH:8]=1)[CH3:16])[C:22]([NH2:21])=[O:23]

Participants

5

Reactant 2

HCID 107545733-Butyn-2-amine, 4-[3-(4-fluorophenoxy)phenyl]-N-hydroxy-HCID 11051572Potassio isocyanate

Product 1

HCID 72059Fenleuton

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

The N-[4-(3-(4-fluorophenoxy)phenyl)-3-butyn-2-yl]hydroxylamine prepared in step 3 above was taken up in ethyl acetate (36 kg) and cooled to 5° C. A solution of freshly prepared potassium isocyanate (10 kg) in water (18 kg) was slowly added and the exotherimic reaction was maintained below 10° C. The reaction mixture was agitated for 30 min. The layers were separated and the organic phase was dried over MgSO4 and filtered. The filtrate was diluted with heptane (58 kg) and agitated for one hour. The resulting crude product was filtered, dissolved in 45° C. ethyl acetate (42 kg). PWA carbon (0.5 kg) and Ultra Norit C (0.5 kg) were added and the mixture was agitated for 30 minutes and filtered. The combined filtrate and washings were diluted with heptane (68 kg) and filtered to provide N-hydroxy-N-[4-(3-(4-fluorophenoxy)phenyl)-3-butyn-2-yl]urea (2.94 kg). m.p. 139°-40° C.; 1H NMR (d6Me2SO) 1.33 (d, 3, J=7 Hz), 5.10 (q, 1, J=7 Hz), 6.55 (s, 2), 6.87 (m, 1), 7.03 (m, 1), 7.13 (m, 3), 7.25 (t, 2, J=8 Hz), 7.37 (t, 1, J=8 Hz), 9.33 (s, 1) ppm; mass spectrum m/e (rel intensity) 332 (80, M+ +NH4), 315 (75, M+ +H), 289 (80), 272 (100). Analysis calculated for C17 H15FN2O3 : C, 64.95, H, 4.81, N, 8.91; found: C, 64.67, H, 4.76, N, 8.81.

Workup

  1. customthe exotherimic reaction
  2. temperaturewas maintained below 10° C
  3. customThe layers were separated
  4. dry with materialthe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. additionThe filtrate was diluted with heptane (58 kg)
  7. stirringagitated for one hour
  8. filtrationThe resulting crude product was filtered
  9. dissolutiondissolved in 45° C. ethyl acetate (42 kg)
  10. additionPWA carbon (0.5 kg) and Ultra Norit C (0.5 kg) were added
  11. stirringthe mixture was agitated for 30 minutes
  12. filtrationfiltered
  13. additionThe combined filtrate and washings were diluted with heptane (68 kg)
  14. filtrationfiltered

Sources & evidence

ORD record
ord-d1f728fddee74a5e93347735ec28da9a
Source dataset
uspto-grants-1998_02
Patent number
US05714633

Reaction notes

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