Deflazacort

As per the process of TR Bromo

A solution of 1part of 3TR bromo,0.6 part of tert butylhydroperoxide and 0.05 part of 35% solution
of benzyltrimethylammoniumhydroxide and 5.3 part of toluene stir for 12 hrs at 40 degree cen.Add
brine solution after reaction and extracted with ………1,4-dioxane.

Further 11 hydroxy has to be made as per usual process.

 20-Carboethoxyhydrazone of 1,4-pregnadiene-11-hydroxy-16α,17α-epoxy-3-one (13)

To a stirring suspension of 11 hydroxy epoxide (0.50 g, 1.25 mmol) in anhydrous 1,4-dioxane

(24 mL), ethyl carbazate (0.26 g, 2.5 mmol) and p-toluenesulfonic acid (0.24 g, 1.25 mmol)
were sequentially added at room temperature under argon atmosphere. The resulting
mixture was stirred at the same temperature for 8 h. Then aq. NaHCO3 was added and the
mixture extracted with EtOAc; the organic layer was dried (Na2SO4) and the solvent
evaporated under reduced pressure. The solid residue was recrystallized from Et2O to give
the final compound protected material (0.36 g, 59% yield) as a white solid. 1H NMR (500
MHz): δ 1.01–1.12 (m, 2H), 1.15–1.27 (m, 2H), 1.31 (s, 3H), 1.33 (t, J = 7.1, 3H), 1.40–1.44
(m, 1H), 1.47 (s, 3H), 1.68 (dd, J = 3.1, 14.2, 1H), 1.96–2.04 (m, 2H), 2.13 (s, 3H), 2.15–2.18
(m, 1H), 2.32 (dd, J = 3.0, 12.7, 1H), 2.50–2.61 (m, 2H), 3.67 (s, 1H), 4.22–4.29 (m, 2H), 4.31
(d, J = 13.1, 1H), 4.40 (bs, 1H), 4.56 (d, J = 13.1, 1H), 6.00 (bs, 1H), 6.25 (d, J = 10.1, 1H), 7.29
(d, J = 10.1, 1H). 13C NMR (125 MHz): 14.6, 18.2, 20.6, 21.2, 27.2, 29.9, 31.9, 33.5, 41.4,
41.7, 44.2, 45.9, 55.0, 56.2, 59.6, 62.1, 69.8, 70.2, 122.5, 127.8, 142.5, 153.6, 156.2, 169.7,
171.2, 186.6. Anal. calcd for C26H34N2O7: C, 64.18; H, 7.04; N 5.76. Found: C, 64.29; H,
7.02; N 5.75.
20-Carboethoxyhydrazone of 1,4-pregnadiene-17α-amino-11,16α-diol-3-one (16)

Method A. Protected Epoxide (0.30 g, 0.62 mmol) was dissolved in anhydrous 1,4-dioxane (15 mL)
under nitrogen atmosphere at rt. Anhydrous ammonia was then gently bubbled into the solution for
3 minutes and the reaction was stirred at the same temperature for 18 h. Nitrogen was bubbled in
the reaction mixture until the ammonia was eliminated from the solution (pH = 7). The mixture was
diluted with CH2Cl2 and the organic layers were washed with brine, dried (Na2SO4) and
concentrated under reduced pressure. The solid residue was recrystallized from Et2O to give the
final compound 16 (0.30 g, 97% yield) as a white solid. Method B (one-pot procedure). To a stirred
suspension of 10 (0.50 g, 1.25 mmol) in anhydrous 1,4-dioxane (24 mL), ethyl carbazate (0.26 g, 2.5
mmol) and p-toluenesulfonic acid (0.24 g, 1.25 mmol) were sequentially added at room temperature
under argon atmosphere. The resulting mixture was stirred at the same temperature for 8 h and
then anhydrous ammonia was gently bubbled into the solution for 3 minutes. The reaction mixture
was stirred at room temperature for 18 h. The mixture was diluted with CH2Cl2 and the organic
layers washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The solid
residue was recrystallized from Et2O to give the final compound 16 (0.43 g, 69% overall yield). 1H
NMR (400 MHz, acetone-d6): δ 1.04–1.16 (m, 5H), 1.21–1.41 (m, 4H), 1.51 (s, 3H), 1.52–1.57 (m, 1H),
1.78–1.99 (m, 4H), 2.03–2.17 (m, 7H), 2.35 (dd, J = 3.4, 13.4, 1H), 2.62 (td, J = 4.9, 13.4, 1H), 3.81 (bs,
1H), 4.17 (q, J = 7.1, 2H), 4.47 (bs, 1H), 4.76 (d, J = 13.0, 1H), 4.90 (d, J = 13.0, 1H), 5.16 (dd, J = 3.0,
9.2, 1H), 5.92 (bs, 1H), 6.14 (dd, J = 1.6, 10.1, 1H), 7.33 (d, J = 10.1, 1H). 13C NMR (100 MHz, acetone-
d6): 14.0, 18.2, 19.9, 20.8, 29.7, 30.9, 31.6, 33.9, 40.9, 44.0, 46.4, 48.9, 55.6, 58.2, 60.8, 69.4, 81.2,
83.7, 121.8, 127.3, 149.4, 153.6, 155.9, 170.1, 170.3, 185.1. Anal. calcd for C26H37N3O7: C, 62.01; H,
7.41; N 8.34. Found: C, 62.08; H, 7.38; N 8.36.
 20-Carboethoxyhydrazone of 1,4-pregnadiene-11-hydroxy- 16α,17α-oxazole-3-one (17)

I2 (0.30 g, 1.19 mmol) was added to a stirred solution of polymer supported

triphenylphosphine (PS-TPP; 100–200 mesh, extent of labeling: ∼3 mmol g−1 triphenylphosphine
loading) (0.40 g, 1.19 mmol) in anhydrous DCM (20 mL) at rt. Then glacial acetic acid (35 μL, 0.59
mmol) was added and the solution was stirred at room temperature for 20′. Afterwards, 16 (0.30 g,
0.59 mmol) and imidazole (0.16 g, 2.38 mmol) were sequentially added and the solution was
warmed to 40 °C and stirred for 2 h. The mixture was then filtered and the solvent removed under
reduced pressure. The solid residue was recrystallized from Et2O to give the final compound 17 (0.29
g, 96% yield) as a white solid. 1H NMR (500 MHz, acetone-d6): δ 1.04 (dd, J = 3.7, 11.4, 1H), 1.07 (s,
1H), 1.09–1.18 (m, 1H), 1.27 (t, J = 7.1, 1H), 1.29–1.36 (m, 3H), 1.51 (s, 3H), 1.74 (dd, J = 5.7, 13.6,
1H), 1.81 (dd, J = 7.6, 13.6, 1H), 1.85–1.90 (m, 4H), 2.12 (s, 3H), 2.18–2.25 (m, 1H), 2.35 (dd, J = 3.4,
13.5, 1H), 2.65 (td, J = 5.7, 13.5, 1H), 3.83 (bs, 1H), 4.17 (q, J = 7.1, 2H), 4.47 (bs, 1H), 4.73 (d, J = 13.0,
1H), 4.92 (d, J = 13.0, 1H), 5.66 (d, J = 5.7, 1H), 5.92 (bs, 1H), 6.14 (dd, J = 1.8, 10.1, 1H), 7.31 (d, J =
10.1, 1H), 9.37 (bs, 1H). 13C NMR (125 MHz, acetone-d6): 13.2, 14.0, 19.1, 19.9, 20.8, 29.7, 30.6,
31.5, 33.9, 41.7, 43.9, 47.0, 50.4, 55.5, 57.5, 60.9, 69.1, 83.7, 91.6, 121.9, 127.4, 145.9, 153.4, 155.7,
165.1, 169.5, 170.2, 185.0. Anal. calcd for C28H37N3O7: C, 63.74; H, 7.07; N 7.96. Found: C, 63.81; H,
7.02; N 7.99.

Deflazacort

To a stirred solution of 17 (0.30 g, 0.57 mmol) in acetone (8 mL), HCl 37% solution (0.09 mL,
1.14 mmol) was added and stirring at room temperature for 24 h. Then aq. NaHCO3 was added and
the mixture extracted with CH2Cl2; the combined organic layers were washed with brine, dried
(Na2SO4) and the solvent evaporated under reduced pressure. Chromatography of the crude
residue over silica gel (hexane : acetone = 7 : 3) gave the pure DFZ (5) (0.18 g, 72% yield) as a white
solid. 1H NMR (400 MHz, CD3OD): δ 1.01 (dd, J = 3.6, 11.3, 1H), 1.02 (s, 3H), 1.06–1.25 (m, 2H), 1.49
(s, 3H), 1.75 (dd, J = 5.9, 13.8, 1H), 1.79–1.85 (m, 1H), 1.89 (dd, J = 3.9, 14.2, 1H), 1.97 (s, 3H), 2.01
(dd, J = 2.7, 13.8, 1H), 2.06–2.12 (m, 1H), 2.13 (s, 3H), 2.20 (dd, J = 4.1, 11.6, 1H), 2.37 (ddd, J = 1.8,
4.6, 13.4, 1H), 2.65 (td, J = 5.7, 13.4, 1H), 4.41 (dd, J = 3.2, 6.3, 1H), 4.93 (s, 2H), 5.30 (d, J = 5.5, 1H),
6.00 (bs, 1H), 6.25 (dd, J = 1.9, 10.1, 1H), 7.45 (d, J = 10.1, 1H). 13C NMR (125 MHz, CD3OD): 12.5,
17.2, 18.9, 20.1, 30.4, 31.6, 33.9, 34.0, 40.9, 44.5, 50.4, 55.5, 67.0, 69.0, 84.8, 94.2, 121.2, 126.5,
158.3, 168.0, 170.6, 172.8, 187.5, 200.9. Anal. calcd for C25H31NO6: C, 68.01; H, 7.08; N 3.17.
Found: C, 68.09; H, 7.06; N 3.15.