Ethanol → Pentoxazone

HRID 2289022Notes

Reaction equation

HRID 2289022 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:6][C:5]([NH:14][C:15](=[O:19])[O:16][CH2:17][CH3:18])=[C:4]([F:20])[CH:3]=1.O[CH:22]([C:28](C)=C)[C:23](OCC)=O.C([OH:33])C.C1(C)C=CC=CC=1>C(N(CCCC)CCCC)CCC.CCCCCC>[Cl:1][C:2]1[C:7]([O:8][CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13]2)=[CH:6][C:5]([N:14]2[C:18](=[O:33])[C:17](=[C:22]([CH3:28])[CH3:23])[O:16][C:15]2=[O:19])=[C:4]([F:20])[CH:3]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 1140TolueneHCID 108555893-Butenoic acid, 2-hydroxy-3-methyl-, ethyl esterHCID 11033971N-[4-Chloro-5-(cyclopentyloxy)-2-fluorophenyl]carbamic acid ethyl ester

Product 1

HCID 11714234PentoxazoneYield 74.5%

Reagents, catalysts & solvents 2

HCID 7622TributylamineCatalystHCID 8058HexaneSolvent

Conditions

Temperature
200 °C

Procedure

Ethyl N-(4-chloro-5-cyclopentyloxy-2-fluorphenyl)carbamate (674 g, 2.24 mmol), ferric chloride (3.7 g, 22.8 mmol) and tributylamine (21 g, 0.113 mol) were introduced into a three-necked flask (3 L) equipped with a mechanical stirrer and a Dean Stark, and the resulting mixture was heated to 200° C. with stirring to form a homogeneous solution. Then, ethyl 2-hydroxy-3-methyl-3-butenoate (484 g, 3.51 mol) was added dropwise over 5.5 hours, and after the addition, the solution was stirred for another 2.5 hours. The ethanol generated during the heating and stirring was distilled away by mean s of the Dean Stark . After completion of the reaction, the reaction mixture was allowed to cool to about 100° C., and then toluene (2.0 L) was added to form a solution. The solution was washed with 1N hydrochloric acid (1 L) and water (1 L). The organic layer was concentrated under reduced pressure, and the resulting oily crude product was crystallized in ethanol (3.85 L) acidified with sulfuric acid. The precipitated crystals were collected by filtration and washed with a small amount of acidic ethanol and then hexane to obtain 3-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)-5-isopropylidene-1,3-oxazolidine-2,4-dione (590 g, yield 74.5%) as white crystals.

Workup

  1. customequipped with a mechanical stirrer
  2. customto form a homogeneous solution
  3. additionafter the addition
  4. stirringthe solution was stirred for another 2.5 hours
  5. stirringstirring
  6. distillationwas distilled away by mean s of the Dean Stark
  7. customAfter completion of the reaction
  8. temperatureto cool to about 100° C.
  9. customto form a solution
  10. washThe solution was washed with 1N hydrochloric acid (1 L) and water (1 L)
  11. concentrationThe organic layer was concentrated under reduced pressure
  12. customthe resulting oily crude product was crystallized in ethanol (3.85 L)
  13. filtrationThe precipitated crystals were collected by filtration
  14. washwashed with a small amount of acidic ethanol

Sources & evidence

ORD record
ord-16d4dd94d7274028a4826d5f4d461645
Source dataset
uspto-grants-2000_07
Patent number
US06090946

Reaction notes

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