Hydroquinone → (4S)-6a-(2,3-difluorophenyl)-4-(trifluoromethyl)hexahydrofuro[3,4-c]isoxazole

HRID 1429617Notes

Reaction equation

HRID 1429617 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9](=[N:19][OH:20])[CH2:10][O:11][C@@H:12]([CH:17]=[CH2:18])[C:13]([F:16])([F:15])[F:14].C1(C=CC(O)=CC=1)O>>[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][C@H:12]([C:13]([F:15])([F:16])[F:14])[CH:17]1[CH2:18][O:20][NH:19]2

Participants

3

Reactant 2

HCID 785HydroquinoneHCID 86668363(S)-1-(2,3-difluorophenyl)-2-((1,1,1-trifluorobut-3-en-2-yl)oxy)ethanone oxime

Product 1

HCID 70495269(4S)-6a-(2,3-difluorophenyl)-4-(trifluoromethyl)hexahydrofuro[3,4-c]isoxazoleYield 77.1%

Conditions

Temperature
140 °C

Procedure

(S)-1-(2,3-difluorophenyl)-2-((1,1,1-trifluorobut-3-en-2-yl)oxy)ethanone oxime (4.10 g) was dissolved in xylenes (40 mL) and hydroquinone (380 mg) was added. The reaction mixture was heated to reflux (heating block temperature 140° C.) for 20 h, then cooled and evaporated. The residue was purified by silica gel column chromatography (1% to 25% EtOAc in hexanes) to obtain the title compound (3.16 g). 1H NMR (400 MHz, CDCl3) δ ppm 3.77 (br. s., 1H), 3.99-4.16 (m, 1H), 4.16-4.22 (m, 1H), 4.22-4.44 (m, 2H), 4.51 (d, J=9.9 Hz, 1H), 5.44 (s, 1H), 7.07-7.24 (m, 2H), 7.38 (br. s., 1H)

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. temperaturecooled
  4. customevaporated
  5. customThe residue was purified by silica gel column chromatography (1% to 25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-aaabfc7a6a81453b990ddcce58d0ded5
Source dataset
uspto-grants-2015_01
Patent number
US08940734B2

Reaction notes

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