Hydroquinone → 6a-(2,3-Difluorophenyl)-4-((trityloxy)methyl)hexahydrofuro[3,4-c]isoxazole

HRID 1855246Notes

Reaction equation

HRID 1855246 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9](=[N:36][OH:37])[CH2:10][O:11][CH:12]([CH:34]=[CH2:35])[CH2:13][O:14][C:15]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1(C=CC(O)=CC=1)O>C1(C)C=CC=CC=1>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]12[CH2:10][O:11][CH:12]([CH2:13][O:14][C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH:34]1[CH2:35][O:37][NH:36]2

Participants

4

Reactant 2

HCID 785HydroquinoneHCID 86724406HCID 86724406, compound

Product 1

HCID 704967636a-(2,3-Difluorophenyl)-4-((trityloxy)methyl)hexahydrofuro[3,4-c]isoxazoleYield 66.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
112.5 °C

Procedure

To a solution of 1-(2,3-Difluorophenyl)-2-(1-(trityloxy)but-3-en-2-yloxy)ethanone oxime 16 (20.0 g, 0.0400 mol, 1.0 equiv.) in toluene (140 mL) was charged hydroquinone (0.0882 g, 0.008 mol, 0.2 equiv.). The reaction mixture was heated to reflux (110-115° C.) and held for 13 hours. The reaction mixture was cooled to 20-25° C. and then concentrated under vacuum (T<45° C.). The solvents were chased with 2-propanol (100 mL). To the crude residue was charged isopropanol (140 mL) and the mixture was heated to 65-70° C. until a clear solution is formed. The solution was cooled to 0° C. at 10° C./hr and then held for 1 hour. The resulting suspension was filtered and the solid was rinsed with cold 2-propanol (40.0). After drying the title compound 17 was obtained as a powder (13.2 g).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureThe reaction mixture was cooled to 20-25° C.
  3. concentrationconcentrated under vacuum (T<45° C.)
  4. additionTo the crude residue was charged isopropanol (140 mL)
  5. temperaturethe mixture was heated to 65-70° C. until a clear solution
  6. customis formed
  7. temperatureThe solution was cooled to 0° C. at 10° C./hr
  8. waitheld for 1 hour
  9. filtrationThe resulting suspension was filtered
  10. washthe solid was rinsed with cold 2-propanol (40.0)
  11. dry with materialAfter drying the title compound 17

Sources & evidence

ORD record
ord-76cc3d4e8caa4f42aa5fd1dfa0f7c16e
Source dataset
uspto-grants-2015_02
Patent number
US08962858B2

Reaction notes

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