(4bR,6bS,9aR,12S)-4b, 12-Difluoro-6b-glycoloyl-5-hydroxy-4a,6a,8,8-tetramethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one → Fluocinolone

HRID 68226Notes

Reaction equation

HRID 68226 reaction equation
[F:1][C@@:2]12[C:29]3([CH3:30])[C:24](=[CH:25][C:26](=[O:31])[CH:27]=[CH:28]3)[C@@H:23]([F:32])[CH2:22][CH:3]1[CH:4]1[C:13]([CH3:17])([CH2:14][CH:15]2[OH:16])[C@:7]2([C:18](=[O:21])[CH2:19][OH:20])[O:8]C(C)(C)[O:10][C@@H:6]2[CH2:5]1>B(F)(F)F.F.O>[F:32][C@@H:23]1[C:24]2[C@:29]([CH3:30])([CH:28]=[CH:27][C:26](=[O:31])[CH:25]=2)[C@:2]2([F:1])[C@H:3]([C@H:4]3[C@:13]([CH3:17])([CH2:14][C@@H:15]2[OH:16])[C@@:7]([OH:8])([C:18](=[O:21])[CH2:19][OH:20])[C@H:6]([OH:10])[CH2:5]3)[CH2:22]1

Participants

4

Reactant 1

HCID 68918594(4bR,6bS,9aR,12S)-4b, 12-Difluoro-6b-glycoloyl-5-hydroxy-4a,6a,8,8-tetramethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one

Product 1

HCID 91488FluocinoloneYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 9855450Trifluoroborane HydrofluorideSolvent

Procedure

(4bR,6bS,9aR,12S)-4b,12-Difluoro-6b-glycoloyl-5-hydroxy-4a,6a,8,8-tetramethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-2-one (10.3 g, 22.76 mmol—commercially available) was suspended in 48% aqueous hydrofluoroboric acid (100 mL) and the resulting suspension stirred at ambient temperature under an atmosphere of nitrogen for 7 hours. The suspension was then diluted with water (200 mL), filtered and the solid washed with water (500 mL). The solid cake was suspended in methanol (200 mL) and concentrated in vacuo. The resulting solid was suspended in tert-butyl-methyl ether (150 mL), filtered and washed with tert-butyl methyl ether (200 mL) to yield the title compound as a white solid, 95% yield, 8.9 g.

Workup

  1. filtrationfiltered
  2. washthe solid washed with water (500 mL)
  3. concentrationconcentrated in vacuo
  4. filtrationfiltered
  5. washwashed with tert-butyl methyl ether (200 mL)

Sources & evidence

ORD record
ord-03f4b2a45e8849539e2a4fb414ccf1cb
Source dataset
uspto-grants-2014_09
Patent number
US08822439B2

Reaction notes

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