Hydrochloric Acid → (-)-Isobutyl 2-[3-(4-Cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetate

HRID 381397Notes

Reaction equation

HRID 381397 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([CH:7]=[N:8][OH:9])=[CH:5][CH:4]=1)#[N:2].ClN1C(=O)CCC1=O.[CH:20]([CH2:22][C:23]([O:25][CH2:26][CH:27]([CH3:29])[CH3:28])=[O:24])=[CH2:21].C(N(CC)CC)C.Cl>O.CN(C=O)C>[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]2[CH2:21][CH:20]([CH2:22][C:23]([O:25][CH2:26][CH:27]([CH3:29])[CH3:28])=[O:24])[O:9][N:8]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 528715Isobutyl but-3-enoateHCID 52147424-Cyanobenzaldehyde oxime

Product 1

HCID 11066048(-)-Isobutyl 2-[3-(4-Cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetateYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
4 °C

Procedure

To a solution of DMF (262.0 L), 4-cyanobenzaldoxime (46 kg, 342.1 mol), and N-chlorosuccinimide (54 kg, 389.4 mol) was added isobutyl vinylacetate (95 kg. 665.7 mol). The solution was cooled to 2-6° C., and triethylamine (40 kg. 388.6 mol) was slowly added over a period of 4 h. The reaction was stirred at the same temperature for an addition 1 h. Water (330.0 L) and hydrochloric acid (1 N, 49 L) were added. The crude product was collected by filtration, washed with water (555.0 L), and redissolved in toluene (500.0 L, 40° C.). The organic layer was washed with water (291.0 L) and dried by azeotropic distillation (removing about 250 L of toluene). Heptane (300.0 L) was added, and the reaction was cooled at 0-5° C. for 3 h. The product was collected by filtration and washed with toluene/heptane (150.0 L, 1/2 ratio). The product was dried under vacuum at 55-60° C. to constant weight: 81.8 kg, 90% yield, mp 98-100° C.; 1H NMR (CDCl3) ∂ 0.96 (6H), 1.96 (1H), 2.70 (1H), 2.92 (1H), 3.15 (1H), 3.56 (1H), 3.90 (2H), 5.20 (1H), 7.70 (2H), 7.80 (2H). Anal. Calcd. for C16H18N2O3: C, 67.12; H, 6.34; N. 9.78. Found: C, 67.06; H, 6.20; N, 9.76.

Workup

  1. filtrationThe crude product was collected by filtration
  2. washwashed with water (555.0 L)
  3. dissolutionredissolved in toluene (500.0 L, 40° C.)
  4. washThe organic layer was washed with water (291.0 L)
  5. dry with materialdried by azeotropic distillation (removing about 250 L of toluene)
  6. additionHeptane (300.0 L) was added
  7. temperaturethe reaction was cooled at 0-5° C. for 3 h
  8. filtrationThe product was collected by filtration
  9. washwashed with toluene/heptane (150.0 L, 1/2 ratio)
  10. customThe product was dried under vacuum at 55-60° C. to constant weight

Sources & evidence

ORD record
ord-f9e2502c668c41199d14882db88c9ac2
Source dataset
uspto-grants-2001_10
Patent number
US06306886B1

Reaction notes

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